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An antigenic chimaera of poliovirus type 1 expressing an epitope from human papillomavirus type 16
Abstracts
Posters: papillomavirus
An antigenic chimaera of poliovirus type 1 expressing an epitope from human papillomavirus type 16 O. Jenkins, A.N. Gillen, K.L. Burke, J. Cason*, D. Patel*, P.S. Shepherd*, D.J. McCance* and J.W. Almond Department of Microbiology, Universityof Reading, London Road, Reading RG15AQ, UK and *Department of Microbiology, Medical School, Guy's Hospital, London SE19RT, UK An antigenic chimaera ofpoliovirus type 1 has been constructed. The amino acids comprising antigenic site 1 of the Sabin 1 strain of poliovirus have been replaced with a 16 amino acid sequence from the major capsid protein of human papillomavirus type 16 (HPVI6). The resulting chimaeric poliovirus is neutralized by monoctonal and polyclonal antibodies raised against the major capsid protein of HPVI6, demonstrating that this sequence is
immunogenic in HPV16 and retains its conformation when expressed on the surface of poliovirus. The chimaera is at present being tested in neutralization and antigen-blocking assays against sera from patients diagnosed with HPV16 infection. Furthermore polyclonal rabbit antisera are being raised to the chimaera to investigate its immunogenic potential.
Session 8: Herpes simplex Herpes simplex vaccines, current status and future prospects Bernard Meignier Institut Mkrieux, 69280 Marcy l'Etoile, France The dominant feature of herpetic diseases is their propensity to recur, due to the reactivation of the virus latent in sensory ganglia. Asymptomatic reactivations are not uncommon and can play an important role in the dissemination of herpetic infections. The cornerstone of a successful prevention of herpes simplex infections is therefore the capacity of vaccines to impede the multiplication of the incoming virus at the portal of entry in the body and to preclude the establishment of latency. The vaccines developed in the past were mostly used to try and cure patients with recurrent disease; such attempts were
never proven to be effective. The few clinical studies carried out so far with subunit vaccines to prevent herpetic infections in carefully designed settings have been disappointing. Current approaches to achieve higher levels of immunity include the use of novel adjuvants with non-replicating antigens or that of genetically engineered live attenuated vaccines. Such materials are protective, at least to some extent, in animal models. The definite evidence of their efficacy will only come from evaluation in clinical trials.
Protection against genital herpes simplex virus (HSV) infection and disease with a recombinant gD glycoprotein vaccine R.L. Burke, G. Van Nest, J. Ostrove* and G. Ott Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA and *NIAID, Bethesda, MD, USA Initial trials with a recombinant subunit gD HSV vaccine given in complete Freund's adjuvant (CFA) with footpad inoculation showed > 9 2 % protection from intravaginal challenge of 5 x 10~p.f.u. of HSV-2 in guinea-pigs and reduced the severity of subsequent spontaneous recurrences. Intramuscular inoculation at 3-week intervals with 6 ~tg of gD with a lipophilic muramyl tripeptide (MTP-PE) produced protection in 60% of animals compared with 50% of those receiving gD in C F A and compared with 0% of control animals receiving adjuvant alone.
Protection correlated with antibody response (r = - 0.82) with 92% of animals who achieved gD ELISA antibody titres > 3000 being protected. Hybridization studies in situ to detect HSV-2 latency associated transcripts were positive in 5/5 control animals and 0/6 uninfected animals compared with 4/19 immunized animals (p<0.05). gD with MTP-PE reduced the frequency of latent infection as well as disease, especially in animals achieving high antibody titres. This combination warrants human trials as a vaccine to prevent genital HSV.
Poor immunogenicity as the reason for the ineffectiveness of a glycoprotein subunit vaccine for genital herpes R. Ashley, R.L. Burke*, J. Benedetti, G. Mertz and L. Corey University of Washington, Seattle, WA 98195, USA and *Chiron Corporation, Emeryville, CA 94608, USA A recently completed double-blind placebo-controlled field trial of an inactivated subunit glycoprotein vaccine (lot 859) administered as three 50 Izg doses of protein at 0, 28 and 140 days to 161 HSV-2 seronegative exposed sexual partners of patients with genital herpes revealed no evidence of vaccine efficacy. None of
184 Vaccine, Vol. 7, April 1989
the HSV seronegative vaccinees who received lot 859 developed HSV-2 neutralizing antibodies /> 1 : 8 after the second and only 36% after the third dose of vaccine; compared with a 92% and 83% seroconversion rate in vaccinees who received an identical dosage schedule of an earlier lot (806) of similarly prepared
Posters: papillomavirus
An antigenic chimaera of poliovirus type 1 expressing an epitope from human papillomavirus type 16 O. Jenkins, A.N. Gillen, K.L. Burke, J. Cason*, D. Patel*, P.S. Shepherd*, D.J. McCance* and J.W. Almond Department of Microbiology, Universityof Reading, London Road, Reading RG15AQ, UK and *Department of Microbiology, Medical School, Guy's Hospital, London SE19RT, UK An antigenic chimaera ofpoliovirus type 1 has been constructed. The amino acids comprising antigenic site 1 of the Sabin 1 strain of poliovirus have been replaced with a 16 amino acid sequence from the major capsid protein of human papillomavirus type 16 (HPVI6). The resulting chimaeric poliovirus is neutralized by monoctonal and polyclonal antibodies raised against the major capsid protein of HPVI6, demonstrating that this sequence is
immunogenic in HPV16 and retains its conformation when expressed on the surface of poliovirus. The chimaera is at present being tested in neutralization and antigen-blocking assays against sera from patients diagnosed with HPV16 infection. Furthermore polyclonal rabbit antisera are being raised to the chimaera to investigate its immunogenic potential.
Session 8: Herpes simplex Herpes simplex vaccines, current status and future prospects Bernard Meignier Institut Mkrieux, 69280 Marcy l'Etoile, France The dominant feature of herpetic diseases is their propensity to recur, due to the reactivation of the virus latent in sensory ganglia. Asymptomatic reactivations are not uncommon and can play an important role in the dissemination of herpetic infections. The cornerstone of a successful prevention of herpes simplex infections is therefore the capacity of vaccines to impede the multiplication of the incoming virus at the portal of entry in the body and to preclude the establishment of latency. The vaccines developed in the past were mostly used to try and cure patients with recurrent disease; such attempts were
never proven to be effective. The few clinical studies carried out so far with subunit vaccines to prevent herpetic infections in carefully designed settings have been disappointing. Current approaches to achieve higher levels of immunity include the use of novel adjuvants with non-replicating antigens or that of genetically engineered live attenuated vaccines. Such materials are protective, at least to some extent, in animal models. The definite evidence of their efficacy will only come from evaluation in clinical trials.
Protection against genital herpes simplex virus (HSV) infection and disease with a recombinant gD glycoprotein vaccine R.L. Burke, G. Van Nest, J. Ostrove* and G. Ott Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA and *NIAID, Bethesda, MD, USA Initial trials with a recombinant subunit gD HSV vaccine given in complete Freund's adjuvant (CFA) with footpad inoculation showed > 9 2 % protection from intravaginal challenge of 5 x 10~p.f.u. of HSV-2 in guinea-pigs and reduced the severity of subsequent spontaneous recurrences. Intramuscular inoculation at 3-week intervals with 6 ~tg of gD with a lipophilic muramyl tripeptide (MTP-PE) produced protection in 60% of animals compared with 50% of those receiving gD in C F A and compared with 0% of control animals receiving adjuvant alone.
Protection correlated with antibody response (r = - 0.82) with 92% of animals who achieved gD ELISA antibody titres > 3000 being protected. Hybridization studies in situ to detect HSV-2 latency associated transcripts were positive in 5/5 control animals and 0/6 uninfected animals compared with 4/19 immunized animals (p<0.05). gD with MTP-PE reduced the frequency of latent infection as well as disease, especially in animals achieving high antibody titres. This combination warrants human trials as a vaccine to prevent genital HSV.
Poor immunogenicity as the reason for the ineffectiveness of a glycoprotein subunit vaccine for genital herpes R. Ashley, R.L. Burke*, J. Benedetti, G. Mertz and L. Corey University of Washington, Seattle, WA 98195, USA and *Chiron Corporation, Emeryville, CA 94608, USA A recently completed double-blind placebo-controlled field trial of an inactivated subunit glycoprotein vaccine (lot 859) administered as three 50 Izg doses of protein at 0, 28 and 140 days to 161 HSV-2 seronegative exposed sexual partners of patients with genital herpes revealed no evidence of vaccine efficacy. None of
184 Vaccine, Vol. 7, April 1989
the HSV seronegative vaccinees who received lot 859 developed HSV-2 neutralizing antibodies /> 1 : 8 after the second and only 36% after the third dose of vaccine; compared with a 92% and 83% seroconversion rate in vaccinees who received an identical dosage schedule of an earlier lot (806) of similarly prepared