- Email: [email protected]
Sweet vaccine against E. coli O157
news
PSTT Vol. 1, No. 2 May 1998
update
Sweet vaccine against E. coli O157 David Bradley, tel/fax: +44 1954 202218, Web: http://www.camsoft.com/elemental/
US scientists have developed an experimental vaccine against the killer bug Escherichia coli O157. Although further clinical trials will be required before the vaccine can be declared protective in humans, the scientists are also looking at its potential for mass vaccination of cattle to eliminate the pathogen at source. Food poisoning by this bacterium has been the major international ‘food scare’ story in recent months, and there have been several instances. • The worst single outbreak occurred in Scotland where, by January 1998, 18 elderly people had died and approximately 500 others had been taken ill • In the summer of 1996, 10,000 Japanese were affected and there were 12 deaths • There have been an estimated 20,000 cases in the USA, with 250 associated deaths E. coli O157 particularly affects the young and the elderly. The most critical effects are haemorrhagic colitis (resulting in bloody diarrhoea) and haemolytic uraemic syndrome, which can result in kidney damage and, possibly, kidney failure. The bacterium lives in cattle and other domesticated species without causing symptoms; contamination of meat during butchering is considered the primary source of the pathogen, although cross contamination from animal faeces is also possible.
Conjugation process To make an effective vaccine, scientists from the National Institutes of Health (NIH), National Institute of Child Health and Human Development (Bethesda, MD, USA) chemically linked (conjugated) a bacterial-surface-polysaccharide antigen (the zero-specific polysaccharide of lipopolysaccharide) from the bacterium to the genetically inactivated protein toxin from another bacterium, Pseudomonas aeruginosa. This conjugation process boosts the efficacy of the polysaccharide as a vaccine, and the same group of scientists applied the principle to eradicating Haemophilus influenzae type b, which causes meningitis in children. Immunological response Dr Szu Shousun and colleagues at the NIH and the Carolinas Medical Center (NC, USA) found that volunteers vaccinated in a clinical trial were able to produce enough antibody to E. coli O157 to kill the microorganism in vitro. More than 80% of 87 volunteers responded with a fourfold increase in immunoglobulin G against this antigen one week after vaccination. Significantly, all volunteers had responded with the same increase after four weeks and the team found that the immunological response was sustained for at least six months. The only side effect was a mild skin reaction (erythema) at the injection site in some volunteers. The researchers report their results in
more detail in the February issue of the Journal of Infectious Diseases1. The researchers point out that zero-specific polysaccharide cannot induce an antibody response in humans. Proteins, on the other hand, are effective antigens at all ages, which is why, the team says, conjugating polysaccharides to proteins is such an important advance in making vaccines. The immune system of recipients of the conjugate vaccine makes antibodies against the bacterial-surface polysaccharide as if it were a protein. Supplanting antibiotic therapy E. coli O157 has been found to be a very persistent microorganism, surviving in animal faeces and even on dry surfaces for periods of months. Patients with haemolytic uraemic syndrome do not respond well to antibiotic treatment, so vaccination could be very important for those at risk and in the control of an outbreak. Indeed, the researchers point out that antibiotics may actually increase symptoms by releasing toxins as the bacteria are lysed. The researchers add that they are soon to move on from this Phase I study to Phase II in children. Reference 01 Shouson, S. et al. (1998) J. Infect. Dis. 177, 383–387
Oral vaccines from plants Adrian Smith, Pharmaceutical Science & Technology Today, tel: +44 1223 315961, fax: +44 1223 464430, e-mail: [email protected]
Axis Genetics recently announced details of licensing agreements signed with US agribusiness and biotechnology company Mycogen Corporation, for 11 families of patents. The agreements grant Axis a nonexclusive licence for human health applications of technology to
alter plants genetically to produce vaccines for oral delivery. Axis will pay annual licence fees and royalties upon commercialization of edible vaccine products. Eight out of the 11 patents cover the use of viral subgenomic promoters, transfer vectors,
Copyright ©1998 Elsevier Science Ltd. All rights reserved. 1461-5347/98/$19.00
hybrid RNA viruses and methods of inserting viral DNA into plant material, and the viral engineering patents allow Axis to proceed in the development of vaccines for cancers, autoimmunity, allergies and infectious diseases for either human or animal use.
47
PSTT Vol. 1, No. 2 May 1998
update
Sweet vaccine against E. coli O157 David Bradley, tel/fax: +44 1954 202218, Web: http://www.camsoft.com/elemental/
US scientists have developed an experimental vaccine against the killer bug Escherichia coli O157. Although further clinical trials will be required before the vaccine can be declared protective in humans, the scientists are also looking at its potential for mass vaccination of cattle to eliminate the pathogen at source. Food poisoning by this bacterium has been the major international ‘food scare’ story in recent months, and there have been several instances. • The worst single outbreak occurred in Scotland where, by January 1998, 18 elderly people had died and approximately 500 others had been taken ill • In the summer of 1996, 10,000 Japanese were affected and there were 12 deaths • There have been an estimated 20,000 cases in the USA, with 250 associated deaths E. coli O157 particularly affects the young and the elderly. The most critical effects are haemorrhagic colitis (resulting in bloody diarrhoea) and haemolytic uraemic syndrome, which can result in kidney damage and, possibly, kidney failure. The bacterium lives in cattle and other domesticated species without causing symptoms; contamination of meat during butchering is considered the primary source of the pathogen, although cross contamination from animal faeces is also possible.
Conjugation process To make an effective vaccine, scientists from the National Institutes of Health (NIH), National Institute of Child Health and Human Development (Bethesda, MD, USA) chemically linked (conjugated) a bacterial-surface-polysaccharide antigen (the zero-specific polysaccharide of lipopolysaccharide) from the bacterium to the genetically inactivated protein toxin from another bacterium, Pseudomonas aeruginosa. This conjugation process boosts the efficacy of the polysaccharide as a vaccine, and the same group of scientists applied the principle to eradicating Haemophilus influenzae type b, which causes meningitis in children. Immunological response Dr Szu Shousun and colleagues at the NIH and the Carolinas Medical Center (NC, USA) found that volunteers vaccinated in a clinical trial were able to produce enough antibody to E. coli O157 to kill the microorganism in vitro. More than 80% of 87 volunteers responded with a fourfold increase in immunoglobulin G against this antigen one week after vaccination. Significantly, all volunteers had responded with the same increase after four weeks and the team found that the immunological response was sustained for at least six months. The only side effect was a mild skin reaction (erythema) at the injection site in some volunteers. The researchers report their results in
more detail in the February issue of the Journal of Infectious Diseases1. The researchers point out that zero-specific polysaccharide cannot induce an antibody response in humans. Proteins, on the other hand, are effective antigens at all ages, which is why, the team says, conjugating polysaccharides to proteins is such an important advance in making vaccines. The immune system of recipients of the conjugate vaccine makes antibodies against the bacterial-surface polysaccharide as if it were a protein. Supplanting antibiotic therapy E. coli O157 has been found to be a very persistent microorganism, surviving in animal faeces and even on dry surfaces for periods of months. Patients with haemolytic uraemic syndrome do not respond well to antibiotic treatment, so vaccination could be very important for those at risk and in the control of an outbreak. Indeed, the researchers point out that antibiotics may actually increase symptoms by releasing toxins as the bacteria are lysed. The researchers add that they are soon to move on from this Phase I study to Phase II in children. Reference 01 Shouson, S. et al. (1998) J. Infect. Dis. 177, 383–387
Oral vaccines from plants Adrian Smith, Pharmaceutical Science & Technology Today, tel: +44 1223 315961, fax: +44 1223 464430, e-mail: [email protected]
Axis Genetics recently announced details of licensing agreements signed with US agribusiness and biotechnology company Mycogen Corporation, for 11 families of patents. The agreements grant Axis a nonexclusive licence for human health applications of technology to
alter plants genetically to produce vaccines for oral delivery. Axis will pay annual licence fees and royalties upon commercialization of edible vaccine products. Eight out of the 11 patents cover the use of viral subgenomic promoters, transfer vectors,
Copyright ©1998 Elsevier Science Ltd. All rights reserved. 1461-5347/98/$19.00
hybrid RNA viruses and methods of inserting viral DNA into plant material, and the viral engineering patents allow Axis to proceed in the development of vaccines for cancers, autoimmunity, allergies and infectious diseases for either human or animal use.
47