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Lower immunity to poliomyelitis viruses in Australian young adults not eligible for inactivated polio vaccine
Vaccine xxx (xxxx) xxx
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Lower immunity to poliomyelitis viruses in Australian young adults not eligible for inactivated polio vaccine Alexandra J. Hendry a,⇑, Frank H. Beard a,b, Aditi Dey a,b, Helen Quinn a,b, Linda Hueston c, Dominic E. Dwyer c, Peter B. McIntyre a a b c
National Centre for Immunisation Research and Surveillance, Children’s Hospital at Westmead, Sydney, Australia University of Sydney, Sydney, Australia Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead, Sydney, Australia
a r t i c l e
i n f o
Article history: Received 2 September 2019 Received in revised form 23 January 2020 Accepted 27 January 2020 Available online xxxx Keywords: Poliomyelitis Polio Inactivated polio vaccine Serosurveillance Serosurvey Immunity Australia
a b s t r a c t There are limited long-term data on seroprevalence of neutralising antibody (nAb) to the three poliovirus serotypes following the switch from oral polio vaccine (OPV) to inactivated polio vaccine (IPV). In Australia, combination vaccines containing IPV replaced OPV in late 2005. Using serum and plasma specimens collected during 2012 and 2013, we compared prevalence of nAb to poliovirus type 1 (PV1), type 2 (PV2) and type 3 (PV3) in birth cohorts with differing IPV and OPV eligibility from an Australian population-based sample. In the total sample of 1673 persons aged 12 months to 99 years, 85% had nAb against PV1, 83% PV2 and 67% PV3. In the cohort 12 to <18 years (eligible for 4 OPV doses, last dose 8–14 years prior), a significantly lower proportion had nAb than in the 7 to <12 year cohort (eligible for 3 OPV doses and an IPV booster, last dose 3–8 years prior) for all poliovirus types: [PV1: 87.1% vs. 95.9% (P = 0.01), PV2: 80.4% vs. 92.9% (P = 0.003) and PV3: 38.1% vs. 84.0% (P < 0.0001)]. These data suggest individual-level immunity may be better maintained when an OPV primary schedule is boosted by IPV, and support inclusion of an IPV booster in travel recommendations for young adults who previously received only OPV. Ó 2020 Elsevier Ltd. All rights reserved.
1. Introduction Poliomyelitis is a disease caused by the highly infectious poliovirus, an enterovirus belonging to the Picornaviridae family [1,2]. There are three serotypes of poliovirus: type 1, type 2 or type 3. Transmission of polioviruses is primarily person-to-person, predominantly by the faecal-oral route, and less frequently by contaminated food or water [3,4]. In countries with high levels of sanitation, transmission via the pharyngeal (respiratory/oral-oral) route may be relatively more important [4]. The virus enters through the mouth, multiplies in the intestine and is excreted in the stools [1–3]. Infection remains asymptomatic in around 95% of cases, but poliovirus can invade the anterior horn cells of the spinal cord, leading to muscle weakness and acute flaccid paralysis [2]. Since the World Health Organization (WHO) launched the global polio eradication initiative in 1988, the incidence of polio cases ⇑ Corresponding author at: National Centre for Immunisation Research and Surveillance, Kids Research Institute, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia. E-mail address: [email protected] (A.J. Hendry).
has decreased by more than 99% [3]. Wild poliovirus type 2 has not been detected since 1999, and was declared eradicated in September 2015 [5]. The last wild poliovirus type 3 case was detected in Nigeria in November 2012 [6]. Wild poliovirus type 1 is the only serotype still in circulation, with transmission persisting in just two countries as at July 2019, Afghanistan and Pakistan [7–9]. The last laboratory-confirmed case of locally acquired polio in Australia was in 1967 [10] and the last imported case in 2007 [11]. The Western Pacific region of the WHO, of which Australia is a member state, was certified polio-free in 2000 [12–15]. Vaccination against poliomyelitis, using Salk trivalent inactivated polio vaccine (IPV), was introduced in Australia in 1955 followed, in 1966, by Sabin trivalent oral polio vaccine (OPV). When OPV was introduced, it was promoted for use in people of all ages, irrespective of whether they had previously had IPV, as well as for infant vaccination. OPV vaccine was used exclusively from 1966, and between 1994 and 2002 there was a funded OPV booster dose for 15–19 year olds [16]. In November 2005, OPV was replaced with IPV-containing combination vaccines. Currently, children in Australia receive four doses of IPV-containing combination vaccines through the National Immunisation Program 3 doses at 2,
https://doi.org/10.1016/j.vaccine.2020.01.080 0264-410X/Ó 2020 Elsevier Ltd. All rights reserved.
Please cite this article as: A. J. Hendry, F. H. Beard, A. Dey et al., Lower immunity to poliomyelitis viruses in Australian young adults not eligible for inactivated polio vaccine, Vaccine, https://doi.org/10.1016/j.vaccine.2020.01.080
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4 and 6 months of age and a booster dose at 4 years of age [17]. Changes in the poliovirus immunisation schedule and estimated coverage are summarised in Table 1. Circulating vaccine-derived polioviruses, predominantly type 2 but also type 1 and (least frequently) type 3 in the trivalent OPV vaccine, can cause paralytic polio in communities with low OPV vaccine coverage [2,18,19], but paralytic cases have been rare in the Western Pacific region until identified in Papua New Guinea in 2018 [20] and in Indonesia [21] and the Philippines in 2019 [22]. To diminish this risk, the updated Polio Eradication and Endgame Strategic Plan 2013–2018 [23] called for a global switch from trivalent to bivalent OPV (containing only types 1 and 3), implemented from April 2016 [24]. Until global eradication of all poliovirus serotypes is achieved, countries remain at risk of polio importation [25,26]. Although age-appropriate coverage for polio vaccines has been relatively high in Australia, exceeding 90% at 12 months of age since 2000 [27,28], seroprevalence of poliovirus-specific antibodies provides otherwise unavailable information about population immunity to polioviruses across a wider age span. Data from the first national serosurvey conducted in Australia between 1996 and 1999, when OPV was in use, suggested that prevalence of presumptive immunity to poliovirus was sufficient to prevent generalised outbreaks due to serotypes 1 and 2, but possibly not for type 3 [29]. Seven years after OPV was replaced with IPV in late 2005 (2012/2013), we aimed to measure specific immunity to poliovirus types 1, 2 and 3 in Australia, in the absence of environmental circulation of OPV vaccine-derived viruses.
2. Methods We randomly sampled 1673 serum and plasma specimens from a bank of 12,411 specimens collected opportunistically from 32 diagnostic laboratories in the private and public sector throughout Australia in 2012 and 2013, as previously described [30]. Information available for each specimen included sex, age or date of birth, residential postcode and date of collection. Information about vaccination history or Indigenous status was not available as it is not recorded on laboratory request forms. Specimens collected from individuals known to be infected with human immunodeficiency virus, otherwise immunocompromised, or to have received multiple transfusions in the three months before specimen collection were excluded. Collection procedures ensured the bank of specimens was sufficient to allow selection for testing proportionate
to census data for gender and rurality within each age group in each of the eight Australian states and territories, with further validation from an Australian study comparing opportunistic and random cluster sampling for estimation of measles immunity [31]. Ethical approval was obtained from the Western Sydney Human Research Ethics Committee, the South Australian Department of Health Human Research Ethics Committee, Melbourne Health Human Research Ethics Committee and the Government of Western Australia Child and Adolescent Health Service Research Ethics Committee. 2.1. Sample size calculation Having previously demonstrated a high correlation between timing of vaccination policy changes and age-specific population immunity to rubella and measles [32], we similarly examined specific age groups matching temporal changes in poliovirus vaccination in Australia [16] (Table 1). Children under one year of age were excluded due to varying completion of the primary vaccination schedule. Sample sizes were calculated based on the anticipated number of specimens likely to be able to be collected, as well as the expected proportions seropositive for poliovirus types 1, 2 and 3 in each age group. The calculated sample sizes were proportional to the 2011 Australian population by region, age and gender, sufficient to achieve 7% precision around our point estimate true immune proportion, with 95% confidence. 2.2. Neutralising antibody assay Neutralising antibody titres to poliovirus types 1, 2 and 3 were measured using a modification of the micro-neutralisation assay method used in the previous serosurvey [29]. Sera were heat inactivated at 56 °C for 30 min before testing. One hundred doses of each of the three Sabin vaccine poliovirus types, provided by the WHO reference laboratory (Doherty Centre, Melbourne, Australia) were incubated with sera at dilutions of 1:4, 1:8 and 1:16 at 37 °C for one hour. After the addition of a suspension of Vero E6 cells, plates were incubated at 37 °C and read microscopically at day four. A virus-free control to detect serum cytotoxicity was included for each sample, which was tested in singlicate for each dilution. Included in each 96-well plate (Corning Costar sterile tissue culture plates) were poliovirus titrations (each poliovirus type in quadruplicate), negative and positive control sera (in duplicate) at titres of <4, 4, 8, 16, 32, 64, and 128 derived from volunteers before and after poliovirus vaccination. Neutralisation titres were
Table 1 Poliovirus vaccination schedule by birth cohort and estimated coverage. Age group during 2012/13 serosurvey
Birth cohort
Poliovirus vaccination schedule [16] and (coverage)
1–<4 years (n = 318) 4–<7 years (n = 158) 7–<12 years (n = 169) 12–<18 years (n = 84) 18–<25 years (n = 98) 25–<36 years (n = 160) 36–<47 years (n = 130) 47 years (n = 556)*
2009–2012
3 doses of IPV by 6 months (>90%)
2006–2008
3 doses of IPV by 6 months; IPV at 3.5–4 yrs (>90%)
2001–2005
3 doses of OPV by 6 months; IPV at 4 yrs (>90%)
1995–2000
3 doses of OPV by 6 months; OPV at 4–5 yrs (>85%)
1988–1994
3 doses of OPV by 6 months; OPV at 5 yrs (>80%)
1977–1987
3 doses of OPV in infancy; OPV at 5 yrs and at 15–19 yrs (>80% for 4 doses, adolescent coverage 50%)
1966–1976
3 doses of OPV recommended (coverage >80%)
Pre 1965
3 doses of IPV and IPV booster if born after 1955; catch-up 3 doses of OPV for people of any age strongly promoted in 1966 (coverage for 1 dose high)
NB: All IPVs are trivalent; only trivalent OPVs have been used in Australia. * Further breakdown of this age group: 47–<65 years: n = 180; 65–<80 years: n = 215; 80–100 years: n = 161.
Please cite this article as: A. J. Hendry, F. H. Beard, A. Dey et al., Lower immunity to poliomyelitis viruses in Australian young adults not eligible for inactivated polio vaccine, Vaccine, https://doi.org/10.1016/j.vaccine.2020.01.080
A.J. Hendry et al. / Vaccine xxx (xxxx) xxx
expressed as the reciprocal of the dilution of the last well before the first well showing 90% cytopathic effect (CPE). Titres 4 were classified as neutralising antibody positive, and indicative of poliovirus immunity. 2.3. Data analysis All-age estimates of the proportion seropositive to each poliovirus serotype for the Australian population, as well as age group specific estimates, were calculated, weighted by age group and region of residence as appropriate to match the required sample size. Binomial 95% confidence intervals were calculated for proportions and the chi-square test used to compare proportions seropositive by age group. To account for multiple comparisons, only P values less than or equal to 0.01 were considered significant. All analyses used SAS v9.4. 3. Results 3.1. Population immunity In the 1673 samples tested, the proportion seropositive for poliovirus type 1 and type 2 was similar, at 85.3% [95%CI 83.6– 87.0] and 83.3% [95% CI 81.5–85.1] respectively, but seropositivity for type 3 was substantially lower (66.7% [95%CI 64.4–68.9]) (Fig. 1). Seropositivity was significantly higher in females than males for type 2 (86.5% vs 80.2%, p < 0.001) and type 3 poliovirus (69.2% vs 64.2%, p < 0.03), but there was no gender difference for type 1 (Fig. 1). The proportion of the total sample seropositive for all three serotypes was 56.0% [95% CI 53.6–58.4], while 4.7% [95% CI 3.7–5.7] were seronegative for all types. Females were significantly more likely to be seropositive for all three types than males (60.0% vs 52.0%, p < 0.001). 3.2. Age-specific immunity Seropositivity to poliovirus type 3 was lower than to types 1 and 2 across all age groups (Fig. 2). The applicable polio vaccine schedule for each age group is shown in Fig. 2, with the key change moving from OPV to IPV vaccine in late 2005; IPV was used from 1955, until replaced by OPV in 1966. Other changes to the number
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and nature of booster doses included campaigns to administer IPV to broad age groups between 1955 and 1958 [16,29], and national campaigns to promote receipt of three OPV doses by persons of any age post OPV introduction in 1966. The age-specific differences apparent in Fig. 2 are shown in more detail in Table 2, with point estimates and statistical significance in comparison with preceding age groups. The proportion of poliovirus seropositive subjects in the age group 1–<4 years (eligible to receive 3 doses of IPV) was significantly lower than in the age group 4–<7 years (eligible for 4 IPV doses) and the age group 7–<12 years (eligible for an IPV booster post OPV) for all three serotypes. The proportions seropositive in the age groups 12–<18 years and 18–<25 years (eligible for 3 primary OPV doses with a 4th dose of OPV at around 5 years) were similar to each other, but had the lowest proportions seropositive for any age group over 4 years. In particular, seropositivity for all three serotypes was significantly lower than the 7– <12 years age group, most pronounced for type 3, declining from 84% to around 37%, before increasing significantly to 58 to 65% in age groups over 25 years. In the age groups 25–<36 and 36– <46 years, the proportion seropositive was higher across all three serotypes than for 18–<25 year olds, but reached statistical significance only for serotype 1 (36-<47 years) and serotype 3 (25<47 years). In persons 47 years, the proportion seropositive for serotypes 1 and 2 decreased, but significantly so only for serotype 2, with seropositivity for serotype 3 maintained. 4. Discussion In the 2012–2013 national serosurvey, over 80% of the Australian population were seropositive for poliovirus type 1 and type 2, with seropositivity to poliovirus type 3 substantially lower overall (67%) and across all age groups. This is consistent with the known lower immunogenicity of poliovirus type 3 antigens and has been reported in previous serosurveys conducted in Australia [29] and internationally [33–39]. The observed age-related variations in seropositivity to each poliovirus serotype are also consistent with previous reports [29,34,37,38,40]. The higher seropositivity to all three poliovirus types found in the 4–<7 years and 7–<12 years age groups compared to the 1– <4 year olds is consistent with receipt of the booster dose at 4 years of age, as reported from the Netherlands and the United States
Fig. 1. Seropositivity to poliovirus types 1, 2 and 3, for total population and by gender, with 95% confidence intervals, Australia, 2012–2013 serosurvey.
Please cite this article as: A. J. Hendry, F. H. Beard, A. Dey et al., Lower immunity to poliomyelitis viruses in Australian young adults not eligible for inactivated polio vaccine, Vaccine, https://doi.org/10.1016/j.vaccine.2020.01.080
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Fig. 2. Seropositivity to poliovirus types 1, 2 and 3 with 95% confidence intervals by age group and recommended poliovirus vaccine doses*, Australia, 2012–2013 serosurvey. * number and type of poliovirus vaccine doses potentially received for each age group listed along x-axis, according to the vaccination schedules in place during each time period (see Table 1).
Table 2 Summary of differences* in age-specific seropositivity to poliovirus types 1, 2 and 3, Australia (2012–2013 serosurvey). Reference age group
Comparison age group
% seropositive to type 1 poliovirus (p-value)
% seropositive to type 2 poliovirus (p-value)
% seropositive to type 3 poliovirus (p-value)
1–<4 years n = 318
4–<7 years n = 158 7–<12 years n = 169 7–<12 years n = 169 12–<18 years n = 84 12–<18 years n = 84 18–<25 years n = 98 18–<25 years n = 98 25–<36 years n = 160 25–<36 years n = 160 36–<47 years n = 130 36–<47 years n = 130 47 years n = 556 47 years n = 556
79.7% vs 93.0% (p = 0.0002)
80.2% vs 91.8% (p = 0.001) 80.2% vs 92.9% (p = 0.0002) 91.8% vs 92.9% (p = 0.70) 91.8% vs 80.4% (p = 0.01) 92.9% vs 80.4% (p = 0.003) 92.9% vs 77.9% (p = 0.0004) 80.4% vs 77.9% (p = 0.67) 80.4% vs 87.1% (p = 0.17) 77.9% vs 87.1% (p = 0.05) 77.9% vs 89.5% (p = 0.02) 87.1% vs 89.5% (p = 0.53) 87.1% vs 78.7% (p = 0.02) 89.5% vs 78.7% (p = 0.005)
72.5% vs 83.5% (p = 0.008) 72.5% vs 84.0% (p = 0.004) 83.5% vs 84.0% (p = 0.91) 83.5% vs 38.1% (p < 0.0001) 84.0% vs 38.1% (p < 0.0001) 84.0% vs 36.4% (p < 0.0001) 38.1% vs 36.4% (p = 0.81) 38.1% vs 57.5% (p = 0.004) 36.4% vs 57.5% (p = 0.001) 36.4% vs 65.0% (p < 0.0001) 57.5% vs 65.0% (p = 0.20) 57.5% vs 65.9% (p = 0.05) 65.0% vs 65.9% (p = 0.84)
4– <7 years n = 158
7–<12 years n = 169
12–<18 years n = 84
18–<25 years n = 98
25–<36 years n = 160
36–<47 years n = 130 *
79.7% vs 95.9% (p < 0.0001) 93.0% vs 95.9% (p = 0.26) 93.0% vs 87.1% (p = 0.13) 95.9% vs 87.1% (p = 0.01) 95.9% vs 76.6% (p < 0.0001) 87.1% vs 76.6% (p = 0.07) 87.1% vs 85.9% (p = 0.80) 76.6% vs 85.9% (p = 0.06) 76.6% vs 90.4% (p = 0.005) 85.9% vs 90.4% (p = 0.25) 85.9% vs 83.1% (p = 0.40) 90.4% vs 83.1% (p = 0.04)
Significant p values 0.01 in bold.
[34,38]. Seropositivity to all three poliovirus types was similar in the 4–<7 year age group, eligible for primary course of IPV with IPV booster, and the 7–<12 year age group, eligible for a sequential schedule of three OPV doses with an IPV booster at around five years of age (Tables 1 and 2).
In birth cohorts eligible for the same OPV-only schedule of three primary doses with a booster dose at 4–5 years of age (Table 1) adolescents (12–<18 years) and young adults (18–<25 years) the proportion seropositive to each of the three poliovirus types was similar, but significantly lower than the two younger cohorts
Please cite this article as: A. J. Hendry, F. H. Beard, A. Dey et al., Lower immunity to poliomyelitis viruses in Australian young adults not eligible for inactivated polio vaccine, Vaccine, https://doi.org/10.1016/j.vaccine.2020.01.080
A.J. Hendry et al. / Vaccine xxx (xxxx) xxx
eligible to receive one or more IPV doses. In the combined age group (12–<25 years), seropositivity for type 3 (36–38%) was half that for types 1 and 2 (77–87%), consistent with their eligibility for OPV doses only (Table 1), as OPV boosting induces lower mucosal and humoral immune responses than IPV [41–44]. Waning of immunity is also a possible factor, as persons aged 12–<25 years were last eligible to receive OPV at 4–5 years of age (Table 1), when childhood vaccine coverage was lower [45]. As OPV use in Australia ceased at the end of 2005 [16] (i.e. seven years prior to the serosurvey), decreased exposure to OPV strains could also contribute to lower seropositivity in persons aged 12–<25 years. Seropositivity was higher, increasing for serotype 3 from around 37% to>57%, in people aged 25–<46 years age, also eligible only for OPV vaccines (those 25–<36 years also eligible for a booster dose of OPV in adolescence) [16], which argues against waning immunity post OPV as the sole factor at play. In adults older than 47 years, seropositivity was lower for types 1 and 2, but well-maintained for type 3. Multiple factors were potentially operative, including exposure to circulating wild poliovirus (most extensive in those born before 1955 but possible through to 1966) [29,46], receipt of up to 4 IPV doses from birth (1955–1965) and additional OPV doses, available for persons of any age from 1966 [29,47]. This 2012–2013 serosurvey provides the second estimate of immunity to poliovirus for the Australian population. Compared to the initial 1996–1999 serosurvey [29], the point estimate of seropositivity to poliovirus type 1 in the total population increased slightly (from 82% to 85%), but decreased for type 2 and type 3 (from 88% to 83% and from 74% to 67%, respectively). When stratified by age, the only marked difference was for type 3 seropositivity among persons 10 to 19 and 20 to 29 years (the age groups reported in 1996–99 [29]) which declined from 67.9 and 68.9% respectively in 1996–99 to 41.2% and 45.8% (data not shown).
5. Limitations Our study had several limitations. First, this study is ecological and we did not have information on the vaccination status of subjects and relied on inferring this from available population data by birth cohort, with some inevitable imprecision during transition years for immunisation programs. Second, we used opportunistic sampling of ambulant persons who had blood collected for diagnostic purposes rather than systematic sampling of community volunteers, so did not have information on potentially relevant co-morbidities or exposures beyond severe immunocompromise or recent transfusion. However, at a population level, we believe our sampling methods guards against demographic bias and minimises participation bias as the collected specimens were from sera submitted for a wide range of routine pathology tests from a number of large public and private laboratories located throughout Australia that service mostly ambulatory patients. Minimal selection bias using this sampling method has been shown previously [31]. Third, we were not able to directly compare results from this serosurvey with the previous one due to variation in laboratory methods [29]. Nevertheless, it is notable that the age group and serotype with the lowest seropositivity in 1996–1999 corresponds to the OPV only cohort (12 to 24 years) in 2012–2013. The finding of lower seropositivity with an OPV-only schedule is consistent with data from the Netherlands [34], where vaccine coverage is high and 6 doses of IPV have been used since 1957 (at 11 months, 4 years and 9 years of age after 3 infant primary doses), and seroprevalence for type 1 (94.6%; 95%CI 93.9–95.3), type 2 (91.8%; 95% CI 90.9–92.6) and type 3 (84.0%; 95% CI 82.9–85.1) is higher than the current or previous Australian serosurvey [34]. Our findings are consistent with waning immunity in Australian birth cohorts eligible only for a 4 dose OPV-containing schedule (born between
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1966 and 2000) and warrant consideration of IPV boosters as part of travel vaccine recommendations for those born between 1988 and 2000. This is similar to recommendations in comparable circumstances in Italy [39]. 6. Conclusion The low proportion of the Australian population seropositive for poliovirus type 3 is not a major concern, given that wild poliovirus type 3 has not been detected worldwide since November 2012 [6] and was declared globally eradicated on 17 October 2019 [48] as was type 2 in 2015 [5]. However, until global eradication is also achieved for type 1, as well as vaccine derived polioviruses, Australia continues to have a non-negligible risk of poliovirus importation from endemic countries [26]. It is unclear what level of population immunity to poliovirus is required to prevent epidemics of polio, with estimates of the herd immunity threshold ranging from 50 to 95% [46]. In this context, it is important to maintain high vaccine coverage and high quality surveillance for acute flaccid paralysis, supplemented by sentinel enterovirus and environmental surveillance activities, to detect any imported cases and implement appropriate public health actions [49]. It is interesting that the age-related variations in poliovirus seropositivity observed in this study were temporally associated with changes in the Australian vaccination schedule, such as booster timing and the switch from OPV to IPV, with suggestive evidence of waning immunity among birth cohorts with an OPV-only schedule. Remeasurement of seroprevalence, ideally linked to vaccine history data, is needed to more validly evaluate whether this apparent waning is sustained and/or progressive. CRediT authorship contribution statement Alexandra J. Hendry: Data curation, Formal analysis, Writing original draft, Writing - review & editing. Frank H. Beard: Supervision, Writing - original draft, Writing - review & editing. Aditi Dey: Writing - review & editing. Helen Quinn: Supervision, Writing review & editing. Linda Hueston: Methodology, Investigation, Data curation, Writing - review & editing. Dominic E. Dwyer: Conceptualization, Supervision, Writing - review & editing. Peter B. McIntyre: Conceptualization, Supervision, Writing - original draft, Writing - review & editing. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgements We wish to thank the staff of all the laboratories that have contributed sera/plasma to our national serosurvey program for their valuable contribution. The National Centre for Immunisation Research and Surveillance is supported by the Australian Government Department of Health, the NSW Ministry of Health and The Children’s Hospital at Westmead. The opinions expressed in this report are those of the authors, and do not necessarily represent the views of these agencies. References [1] Centers for Disease Control & Prevention. Poliomyelitis. In: Hamborsky J, Kroger A, Wolfe S (editors). Epidemiology and Prevention of VaccinePreventable Diseases. Washington D.C: Public Health Foundation; 2015.
Please cite this article as: A. J. Hendry, F. H. Beard, A. Dey et al., Lower immunity to poliomyelitis viruses in Australian young adults not eligible for inactivated polio vaccine, Vaccine, https://doi.org/10.1016/j.vaccine.2020.01.080
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Please cite this article as: A. J. Hendry, F. H. Beard, A. Dey et al., Lower immunity to poliomyelitis viruses in Australian young adults not eligible for inactivated polio vaccine, Vaccine, https://doi.org/10.1016/j.vaccine.2020.01.080
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Lower immunity to poliomyelitis viruses in Australian young adults not eligible for inactivated polio vaccine Alexandra J. Hendry a,⇑, Frank H. Beard a,b, Aditi Dey a,b, Helen Quinn a,b, Linda Hueston c, Dominic E. Dwyer c, Peter B. McIntyre a a b c
National Centre for Immunisation Research and Surveillance, Children’s Hospital at Westmead, Sydney, Australia University of Sydney, Sydney, Australia Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead, Sydney, Australia
a r t i c l e
i n f o
Article history: Received 2 September 2019 Received in revised form 23 January 2020 Accepted 27 January 2020 Available online xxxx Keywords: Poliomyelitis Polio Inactivated polio vaccine Serosurveillance Serosurvey Immunity Australia
a b s t r a c t There are limited long-term data on seroprevalence of neutralising antibody (nAb) to the three poliovirus serotypes following the switch from oral polio vaccine (OPV) to inactivated polio vaccine (IPV). In Australia, combination vaccines containing IPV replaced OPV in late 2005. Using serum and plasma specimens collected during 2012 and 2013, we compared prevalence of nAb to poliovirus type 1 (PV1), type 2 (PV2) and type 3 (PV3) in birth cohorts with differing IPV and OPV eligibility from an Australian population-based sample. In the total sample of 1673 persons aged 12 months to 99 years, 85% had nAb against PV1, 83% PV2 and 67% PV3. In the cohort 12 to <18 years (eligible for 4 OPV doses, last dose 8–14 years prior), a significantly lower proportion had nAb than in the 7 to <12 year cohort (eligible for 3 OPV doses and an IPV booster, last dose 3–8 years prior) for all poliovirus types: [PV1: 87.1% vs. 95.9% (P = 0.01), PV2: 80.4% vs. 92.9% (P = 0.003) and PV3: 38.1% vs. 84.0% (P < 0.0001)]. These data suggest individual-level immunity may be better maintained when an OPV primary schedule is boosted by IPV, and support inclusion of an IPV booster in travel recommendations for young adults who previously received only OPV. Ó 2020 Elsevier Ltd. All rights reserved.
1. Introduction Poliomyelitis is a disease caused by the highly infectious poliovirus, an enterovirus belonging to the Picornaviridae family [1,2]. There are three serotypes of poliovirus: type 1, type 2 or type 3. Transmission of polioviruses is primarily person-to-person, predominantly by the faecal-oral route, and less frequently by contaminated food or water [3,4]. In countries with high levels of sanitation, transmission via the pharyngeal (respiratory/oral-oral) route may be relatively more important [4]. The virus enters through the mouth, multiplies in the intestine and is excreted in the stools [1–3]. Infection remains asymptomatic in around 95% of cases, but poliovirus can invade the anterior horn cells of the spinal cord, leading to muscle weakness and acute flaccid paralysis [2]. Since the World Health Organization (WHO) launched the global polio eradication initiative in 1988, the incidence of polio cases ⇑ Corresponding author at: National Centre for Immunisation Research and Surveillance, Kids Research Institute, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia. E-mail address: [email protected] (A.J. Hendry).
has decreased by more than 99% [3]. Wild poliovirus type 2 has not been detected since 1999, and was declared eradicated in September 2015 [5]. The last wild poliovirus type 3 case was detected in Nigeria in November 2012 [6]. Wild poliovirus type 1 is the only serotype still in circulation, with transmission persisting in just two countries as at July 2019, Afghanistan and Pakistan [7–9]. The last laboratory-confirmed case of locally acquired polio in Australia was in 1967 [10] and the last imported case in 2007 [11]. The Western Pacific region of the WHO, of which Australia is a member state, was certified polio-free in 2000 [12–15]. Vaccination against poliomyelitis, using Salk trivalent inactivated polio vaccine (IPV), was introduced in Australia in 1955 followed, in 1966, by Sabin trivalent oral polio vaccine (OPV). When OPV was introduced, it was promoted for use in people of all ages, irrespective of whether they had previously had IPV, as well as for infant vaccination. OPV vaccine was used exclusively from 1966, and between 1994 and 2002 there was a funded OPV booster dose for 15–19 year olds [16]. In November 2005, OPV was replaced with IPV-containing combination vaccines. Currently, children in Australia receive four doses of IPV-containing combination vaccines through the National Immunisation Program 3 doses at 2,
https://doi.org/10.1016/j.vaccine.2020.01.080 0264-410X/Ó 2020 Elsevier Ltd. All rights reserved.
Please cite this article as: A. J. Hendry, F. H. Beard, A. Dey et al., Lower immunity to poliomyelitis viruses in Australian young adults not eligible for inactivated polio vaccine, Vaccine, https://doi.org/10.1016/j.vaccine.2020.01.080
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4 and 6 months of age and a booster dose at 4 years of age [17]. Changes in the poliovirus immunisation schedule and estimated coverage are summarised in Table 1. Circulating vaccine-derived polioviruses, predominantly type 2 but also type 1 and (least frequently) type 3 in the trivalent OPV vaccine, can cause paralytic polio in communities with low OPV vaccine coverage [2,18,19], but paralytic cases have been rare in the Western Pacific region until identified in Papua New Guinea in 2018 [20] and in Indonesia [21] and the Philippines in 2019 [22]. To diminish this risk, the updated Polio Eradication and Endgame Strategic Plan 2013–2018 [23] called for a global switch from trivalent to bivalent OPV (containing only types 1 and 3), implemented from April 2016 [24]. Until global eradication of all poliovirus serotypes is achieved, countries remain at risk of polio importation [25,26]. Although age-appropriate coverage for polio vaccines has been relatively high in Australia, exceeding 90% at 12 months of age since 2000 [27,28], seroprevalence of poliovirus-specific antibodies provides otherwise unavailable information about population immunity to polioviruses across a wider age span. Data from the first national serosurvey conducted in Australia between 1996 and 1999, when OPV was in use, suggested that prevalence of presumptive immunity to poliovirus was sufficient to prevent generalised outbreaks due to serotypes 1 and 2, but possibly not for type 3 [29]. Seven years after OPV was replaced with IPV in late 2005 (2012/2013), we aimed to measure specific immunity to poliovirus types 1, 2 and 3 in Australia, in the absence of environmental circulation of OPV vaccine-derived viruses.
2. Methods We randomly sampled 1673 serum and plasma specimens from a bank of 12,411 specimens collected opportunistically from 32 diagnostic laboratories in the private and public sector throughout Australia in 2012 and 2013, as previously described [30]. Information available for each specimen included sex, age or date of birth, residential postcode and date of collection. Information about vaccination history or Indigenous status was not available as it is not recorded on laboratory request forms. Specimens collected from individuals known to be infected with human immunodeficiency virus, otherwise immunocompromised, or to have received multiple transfusions in the three months before specimen collection were excluded. Collection procedures ensured the bank of specimens was sufficient to allow selection for testing proportionate
to census data for gender and rurality within each age group in each of the eight Australian states and territories, with further validation from an Australian study comparing opportunistic and random cluster sampling for estimation of measles immunity [31]. Ethical approval was obtained from the Western Sydney Human Research Ethics Committee, the South Australian Department of Health Human Research Ethics Committee, Melbourne Health Human Research Ethics Committee and the Government of Western Australia Child and Adolescent Health Service Research Ethics Committee. 2.1. Sample size calculation Having previously demonstrated a high correlation between timing of vaccination policy changes and age-specific population immunity to rubella and measles [32], we similarly examined specific age groups matching temporal changes in poliovirus vaccination in Australia [16] (Table 1). Children under one year of age were excluded due to varying completion of the primary vaccination schedule. Sample sizes were calculated based on the anticipated number of specimens likely to be able to be collected, as well as the expected proportions seropositive for poliovirus types 1, 2 and 3 in each age group. The calculated sample sizes were proportional to the 2011 Australian population by region, age and gender, sufficient to achieve 7% precision around our point estimate true immune proportion, with 95% confidence. 2.2. Neutralising antibody assay Neutralising antibody titres to poliovirus types 1, 2 and 3 were measured using a modification of the micro-neutralisation assay method used in the previous serosurvey [29]. Sera were heat inactivated at 56 °C for 30 min before testing. One hundred doses of each of the three Sabin vaccine poliovirus types, provided by the WHO reference laboratory (Doherty Centre, Melbourne, Australia) were incubated with sera at dilutions of 1:4, 1:8 and 1:16 at 37 °C for one hour. After the addition of a suspension of Vero E6 cells, plates were incubated at 37 °C and read microscopically at day four. A virus-free control to detect serum cytotoxicity was included for each sample, which was tested in singlicate for each dilution. Included in each 96-well plate (Corning Costar sterile tissue culture plates) were poliovirus titrations (each poliovirus type in quadruplicate), negative and positive control sera (in duplicate) at titres of <4, 4, 8, 16, 32, 64, and 128 derived from volunteers before and after poliovirus vaccination. Neutralisation titres were
Table 1 Poliovirus vaccination schedule by birth cohort and estimated coverage. Age group during 2012/13 serosurvey
Birth cohort
Poliovirus vaccination schedule [16] and (coverage)
1–<4 years (n = 318) 4–<7 years (n = 158) 7–<12 years (n = 169) 12–<18 years (n = 84) 18–<25 years (n = 98) 25–<36 years (n = 160) 36–<47 years (n = 130) 47 years (n = 556)*
2009–2012
3 doses of IPV by 6 months (>90%)
2006–2008
3 doses of IPV by 6 months; IPV at 3.5–4 yrs (>90%)
2001–2005
3 doses of OPV by 6 months; IPV at 4 yrs (>90%)
1995–2000
3 doses of OPV by 6 months; OPV at 4–5 yrs (>85%)
1988–1994
3 doses of OPV by 6 months; OPV at 5 yrs (>80%)
1977–1987
3 doses of OPV in infancy; OPV at 5 yrs and at 15–19 yrs (>80% for 4 doses, adolescent coverage 50%)
1966–1976
3 doses of OPV recommended (coverage >80%)
Pre 1965
3 doses of IPV and IPV booster if born after 1955; catch-up 3 doses of OPV for people of any age strongly promoted in 1966 (coverage for 1 dose high)
NB: All IPVs are trivalent; only trivalent OPVs have been used in Australia. * Further breakdown of this age group: 47–<65 years: n = 180; 65–<80 years: n = 215; 80–100 years: n = 161.
Please cite this article as: A. J. Hendry, F. H. Beard, A. Dey et al., Lower immunity to poliomyelitis viruses in Australian young adults not eligible for inactivated polio vaccine, Vaccine, https://doi.org/10.1016/j.vaccine.2020.01.080
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expressed as the reciprocal of the dilution of the last well before the first well showing 90% cytopathic effect (CPE). Titres 4 were classified as neutralising antibody positive, and indicative of poliovirus immunity. 2.3. Data analysis All-age estimates of the proportion seropositive to each poliovirus serotype for the Australian population, as well as age group specific estimates, were calculated, weighted by age group and region of residence as appropriate to match the required sample size. Binomial 95% confidence intervals were calculated for proportions and the chi-square test used to compare proportions seropositive by age group. To account for multiple comparisons, only P values less than or equal to 0.01 were considered significant. All analyses used SAS v9.4. 3. Results 3.1. Population immunity In the 1673 samples tested, the proportion seropositive for poliovirus type 1 and type 2 was similar, at 85.3% [95%CI 83.6– 87.0] and 83.3% [95% CI 81.5–85.1] respectively, but seropositivity for type 3 was substantially lower (66.7% [95%CI 64.4–68.9]) (Fig. 1). Seropositivity was significantly higher in females than males for type 2 (86.5% vs 80.2%, p < 0.001) and type 3 poliovirus (69.2% vs 64.2%, p < 0.03), but there was no gender difference for type 1 (Fig. 1). The proportion of the total sample seropositive for all three serotypes was 56.0% [95% CI 53.6–58.4], while 4.7% [95% CI 3.7–5.7] were seronegative for all types. Females were significantly more likely to be seropositive for all three types than males (60.0% vs 52.0%, p < 0.001). 3.2. Age-specific immunity Seropositivity to poliovirus type 3 was lower than to types 1 and 2 across all age groups (Fig. 2). The applicable polio vaccine schedule for each age group is shown in Fig. 2, with the key change moving from OPV to IPV vaccine in late 2005; IPV was used from 1955, until replaced by OPV in 1966. Other changes to the number
3
and nature of booster doses included campaigns to administer IPV to broad age groups between 1955 and 1958 [16,29], and national campaigns to promote receipt of three OPV doses by persons of any age post OPV introduction in 1966. The age-specific differences apparent in Fig. 2 are shown in more detail in Table 2, with point estimates and statistical significance in comparison with preceding age groups. The proportion of poliovirus seropositive subjects in the age group 1–<4 years (eligible to receive 3 doses of IPV) was significantly lower than in the age group 4–<7 years (eligible for 4 IPV doses) and the age group 7–<12 years (eligible for an IPV booster post OPV) for all three serotypes. The proportions seropositive in the age groups 12–<18 years and 18–<25 years (eligible for 3 primary OPV doses with a 4th dose of OPV at around 5 years) were similar to each other, but had the lowest proportions seropositive for any age group over 4 years. In particular, seropositivity for all three serotypes was significantly lower than the 7– <12 years age group, most pronounced for type 3, declining from 84% to around 37%, before increasing significantly to 58 to 65% in age groups over 25 years. In the age groups 25–<36 and 36– <46 years, the proportion seropositive was higher across all three serotypes than for 18–<25 year olds, but reached statistical significance only for serotype 1 (36-<47 years) and serotype 3 (25<47 years). In persons 47 years, the proportion seropositive for serotypes 1 and 2 decreased, but significantly so only for serotype 2, with seropositivity for serotype 3 maintained. 4. Discussion In the 2012–2013 national serosurvey, over 80% of the Australian population were seropositive for poliovirus type 1 and type 2, with seropositivity to poliovirus type 3 substantially lower overall (67%) and across all age groups. This is consistent with the known lower immunogenicity of poliovirus type 3 antigens and has been reported in previous serosurveys conducted in Australia [29] and internationally [33–39]. The observed age-related variations in seropositivity to each poliovirus serotype are also consistent with previous reports [29,34,37,38,40]. The higher seropositivity to all three poliovirus types found in the 4–<7 years and 7–<12 years age groups compared to the 1– <4 year olds is consistent with receipt of the booster dose at 4 years of age, as reported from the Netherlands and the United States
Fig. 1. Seropositivity to poliovirus types 1, 2 and 3, for total population and by gender, with 95% confidence intervals, Australia, 2012–2013 serosurvey.
Please cite this article as: A. J. Hendry, F. H. Beard, A. Dey et al., Lower immunity to poliomyelitis viruses in Australian young adults not eligible for inactivated polio vaccine, Vaccine, https://doi.org/10.1016/j.vaccine.2020.01.080
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Fig. 2. Seropositivity to poliovirus types 1, 2 and 3 with 95% confidence intervals by age group and recommended poliovirus vaccine doses*, Australia, 2012–2013 serosurvey. * number and type of poliovirus vaccine doses potentially received for each age group listed along x-axis, according to the vaccination schedules in place during each time period (see Table 1).
Table 2 Summary of differences* in age-specific seropositivity to poliovirus types 1, 2 and 3, Australia (2012–2013 serosurvey). Reference age group
Comparison age group
% seropositive to type 1 poliovirus (p-value)
% seropositive to type 2 poliovirus (p-value)
% seropositive to type 3 poliovirus (p-value)
1–<4 years n = 318
4–<7 years n = 158 7–<12 years n = 169 7–<12 years n = 169 12–<18 years n = 84 12–<18 years n = 84 18–<25 years n = 98 18–<25 years n = 98 25–<36 years n = 160 25–<36 years n = 160 36–<47 years n = 130 36–<47 years n = 130 47 years n = 556 47 years n = 556
79.7% vs 93.0% (p = 0.0002)
80.2% vs 91.8% (p = 0.001) 80.2% vs 92.9% (p = 0.0002) 91.8% vs 92.9% (p = 0.70) 91.8% vs 80.4% (p = 0.01) 92.9% vs 80.4% (p = 0.003) 92.9% vs 77.9% (p = 0.0004) 80.4% vs 77.9% (p = 0.67) 80.4% vs 87.1% (p = 0.17) 77.9% vs 87.1% (p = 0.05) 77.9% vs 89.5% (p = 0.02) 87.1% vs 89.5% (p = 0.53) 87.1% vs 78.7% (p = 0.02) 89.5% vs 78.7% (p = 0.005)
72.5% vs 83.5% (p = 0.008) 72.5% vs 84.0% (p = 0.004) 83.5% vs 84.0% (p = 0.91) 83.5% vs 38.1% (p < 0.0001) 84.0% vs 38.1% (p < 0.0001) 84.0% vs 36.4% (p < 0.0001) 38.1% vs 36.4% (p = 0.81) 38.1% vs 57.5% (p = 0.004) 36.4% vs 57.5% (p = 0.001) 36.4% vs 65.0% (p < 0.0001) 57.5% vs 65.0% (p = 0.20) 57.5% vs 65.9% (p = 0.05) 65.0% vs 65.9% (p = 0.84)
4– <7 years n = 158
7–<12 years n = 169
12–<18 years n = 84
18–<25 years n = 98
25–<36 years n = 160
36–<47 years n = 130 *
79.7% vs 95.9% (p < 0.0001) 93.0% vs 95.9% (p = 0.26) 93.0% vs 87.1% (p = 0.13) 95.9% vs 87.1% (p = 0.01) 95.9% vs 76.6% (p < 0.0001) 87.1% vs 76.6% (p = 0.07) 87.1% vs 85.9% (p = 0.80) 76.6% vs 85.9% (p = 0.06) 76.6% vs 90.4% (p = 0.005) 85.9% vs 90.4% (p = 0.25) 85.9% vs 83.1% (p = 0.40) 90.4% vs 83.1% (p = 0.04)
Significant p values 0.01 in bold.
[34,38]. Seropositivity to all three poliovirus types was similar in the 4–<7 year age group, eligible for primary course of IPV with IPV booster, and the 7–<12 year age group, eligible for a sequential schedule of three OPV doses with an IPV booster at around five years of age (Tables 1 and 2).
In birth cohorts eligible for the same OPV-only schedule of three primary doses with a booster dose at 4–5 years of age (Table 1) adolescents (12–<18 years) and young adults (18–<25 years) the proportion seropositive to each of the three poliovirus types was similar, but significantly lower than the two younger cohorts
Please cite this article as: A. J. Hendry, F. H. Beard, A. Dey et al., Lower immunity to poliomyelitis viruses in Australian young adults not eligible for inactivated polio vaccine, Vaccine, https://doi.org/10.1016/j.vaccine.2020.01.080
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eligible to receive one or more IPV doses. In the combined age group (12–<25 years), seropositivity for type 3 (36–38%) was half that for types 1 and 2 (77–87%), consistent with their eligibility for OPV doses only (Table 1), as OPV boosting induces lower mucosal and humoral immune responses than IPV [41–44]. Waning of immunity is also a possible factor, as persons aged 12–<25 years were last eligible to receive OPV at 4–5 years of age (Table 1), when childhood vaccine coverage was lower [45]. As OPV use in Australia ceased at the end of 2005 [16] (i.e. seven years prior to the serosurvey), decreased exposure to OPV strains could also contribute to lower seropositivity in persons aged 12–<25 years. Seropositivity was higher, increasing for serotype 3 from around 37% to>57%, in people aged 25–<46 years age, also eligible only for OPV vaccines (those 25–<36 years also eligible for a booster dose of OPV in adolescence) [16], which argues against waning immunity post OPV as the sole factor at play. In adults older than 47 years, seropositivity was lower for types 1 and 2, but well-maintained for type 3. Multiple factors were potentially operative, including exposure to circulating wild poliovirus (most extensive in those born before 1955 but possible through to 1966) [29,46], receipt of up to 4 IPV doses from birth (1955–1965) and additional OPV doses, available for persons of any age from 1966 [29,47]. This 2012–2013 serosurvey provides the second estimate of immunity to poliovirus for the Australian population. Compared to the initial 1996–1999 serosurvey [29], the point estimate of seropositivity to poliovirus type 1 in the total population increased slightly (from 82% to 85%), but decreased for type 2 and type 3 (from 88% to 83% and from 74% to 67%, respectively). When stratified by age, the only marked difference was for type 3 seropositivity among persons 10 to 19 and 20 to 29 years (the age groups reported in 1996–99 [29]) which declined from 67.9 and 68.9% respectively in 1996–99 to 41.2% and 45.8% (data not shown).
5. Limitations Our study had several limitations. First, this study is ecological and we did not have information on the vaccination status of subjects and relied on inferring this from available population data by birth cohort, with some inevitable imprecision during transition years for immunisation programs. Second, we used opportunistic sampling of ambulant persons who had blood collected for diagnostic purposes rather than systematic sampling of community volunteers, so did not have information on potentially relevant co-morbidities or exposures beyond severe immunocompromise or recent transfusion. However, at a population level, we believe our sampling methods guards against demographic bias and minimises participation bias as the collected specimens were from sera submitted for a wide range of routine pathology tests from a number of large public and private laboratories located throughout Australia that service mostly ambulatory patients. Minimal selection bias using this sampling method has been shown previously [31]. Third, we were not able to directly compare results from this serosurvey with the previous one due to variation in laboratory methods [29]. Nevertheless, it is notable that the age group and serotype with the lowest seropositivity in 1996–1999 corresponds to the OPV only cohort (12 to 24 years) in 2012–2013. The finding of lower seropositivity with an OPV-only schedule is consistent with data from the Netherlands [34], where vaccine coverage is high and 6 doses of IPV have been used since 1957 (at 11 months, 4 years and 9 years of age after 3 infant primary doses), and seroprevalence for type 1 (94.6%; 95%CI 93.9–95.3), type 2 (91.8%; 95% CI 90.9–92.6) and type 3 (84.0%; 95% CI 82.9–85.1) is higher than the current or previous Australian serosurvey [34]. Our findings are consistent with waning immunity in Australian birth cohorts eligible only for a 4 dose OPV-containing schedule (born between
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1966 and 2000) and warrant consideration of IPV boosters as part of travel vaccine recommendations for those born between 1988 and 2000. This is similar to recommendations in comparable circumstances in Italy [39]. 6. Conclusion The low proportion of the Australian population seropositive for poliovirus type 3 is not a major concern, given that wild poliovirus type 3 has not been detected worldwide since November 2012 [6] and was declared globally eradicated on 17 October 2019 [48] as was type 2 in 2015 [5]. However, until global eradication is also achieved for type 1, as well as vaccine derived polioviruses, Australia continues to have a non-negligible risk of poliovirus importation from endemic countries [26]. It is unclear what level of population immunity to poliovirus is required to prevent epidemics of polio, with estimates of the herd immunity threshold ranging from 50 to 95% [46]. In this context, it is important to maintain high vaccine coverage and high quality surveillance for acute flaccid paralysis, supplemented by sentinel enterovirus and environmental surveillance activities, to detect any imported cases and implement appropriate public health actions [49]. It is interesting that the age-related variations in poliovirus seropositivity observed in this study were temporally associated with changes in the Australian vaccination schedule, such as booster timing and the switch from OPV to IPV, with suggestive evidence of waning immunity among birth cohorts with an OPV-only schedule. Remeasurement of seroprevalence, ideally linked to vaccine history data, is needed to more validly evaluate whether this apparent waning is sustained and/or progressive. CRediT authorship contribution statement Alexandra J. Hendry: Data curation, Formal analysis, Writing original draft, Writing - review & editing. Frank H. Beard: Supervision, Writing - original draft, Writing - review & editing. Aditi Dey: Writing - review & editing. Helen Quinn: Supervision, Writing review & editing. Linda Hueston: Methodology, Investigation, Data curation, Writing - review & editing. Dominic E. Dwyer: Conceptualization, Supervision, Writing - review & editing. Peter B. McIntyre: Conceptualization, Supervision, Writing - original draft, Writing - review & editing. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgements We wish to thank the staff of all the laboratories that have contributed sera/plasma to our national serosurvey program for their valuable contribution. The National Centre for Immunisation Research and Surveillance is supported by the Australian Government Department of Health, the NSW Ministry of Health and The Children’s Hospital at Westmead. The opinions expressed in this report are those of the authors, and do not necessarily represent the views of these agencies. References [1] Centers for Disease Control & Prevention. Poliomyelitis. In: Hamborsky J, Kroger A, Wolfe S (editors). Epidemiology and Prevention of VaccinePreventable Diseases. Washington D.C: Public Health Foundation; 2015.
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Please cite this article as: A. J. Hendry, F. H. Beard, A. Dey et al., Lower immunity to poliomyelitis viruses in Australian young adults not eligible for inactivated polio vaccine, Vaccine, https://doi.org/10.1016/j.vaccine.2020.01.080