Letters 12
Pittman, M. Neurotoxicity of Bordetalla pertussis. Neurotoxioology 1986, 7, 53 13 Workshop on Acellular Pertussls Vaccine Sponsored by the Intaragency Group to Monitor Vaccine Development, Production and Usage, US Department of Health and Human Services and US Public Health Service (Transcripts available from Dr C.R. Manclark, Center of Biologics Evaluation and Research, 8800 Rockville Pike, Bethesda, MD 20892, USA) 1986, pp. 1-301 14 Robinson, A. and Ashworth, L.A.E. Acellular and defined-component vaccines against pertussis. In: Pathogenesis and Immunity in Pertussis (Eds Wardlaw, A.C. and Patton, R.) John Wiley, Chichester, 1988, pp. 399-417
Gupta, R.K. Development of an improved pertussis vaccine. Ph.D. Thesis Himachal Pradesh University, Shimla, 1987
R.K. G u p t a Visiting Fellow Laboratory of Developmental and Molecular Immunity, NICHD, National Institutes of Health, Bethesda, MD 20892, USA
of proliferative response of T cell activating antigen after exposing bacterial fractions to peripheral blood mononuclear cells (PBMC) from individuals who have recently been infected with shigella is more relevant in the design of the subunit of the vaccine. This new avenue of the above research could also shed important light on protection from shigella infection.
References 1
New approach to develop a vaccine design against shigellosis The development of a vaccine against shigellosis caused by Shioella dysenteriae type 1 is a global intervention strategy for three important reasons- the epidemic potential of the organism, its high virulence and its remarkable ability quickly to acquire resistance to almost all antimicrobial agents. In addition, vaccines against the more common species Shioella sonnei and Shioella flexneri are also required. Immunization by the parenteral route using killed vaccines has been ineffective since they are T cell independent and do not evoke secondary responses on repeated vaccination. F o r more than three decades, several groups of workers ~ have worked on the pathophysiology of the disease and the role of toxin produced by S. dysenteriae 1. So far, available data are not convincing enough to confirm the role of shiga-toxin in the pathogenesis of shigellosis. There are as yet many missing links which need to be explored before rational development of immunoprophylaxis is undertaken. In shigellosis, multi-host factors are responsible for invasion and colonization. Recovery from the disease would primarily depend on development of effective deeper tissue immunity and the role of cellular immunity of the host may be a critical factor in protection against shigellosis, as it is an intracellular pathogen during most of its life cycle. In 1971, streptomycin-dependent attenuated vaccines were widely tested in Yugoslavia 5 and conferred a significant degree of protection in field studies, but these vaccines were somewhat unstable. However, a live vaccine strain can be developed by genetically modifying the pathogen itself so that it loses its virulence but retains immunogenicity. This can be done by identifying the protective antigens of the pathogen and transferring these to a harmless carrier bacterium. Both conventional genetics and recombinant DNA technology can be used to achieve these goals. However, no successful vaccine
410 Vaccine, Vol. 8, August 1990
strain has yet been developed. A carrier based vaccine strain was constructed by isolation of tr~nsconjugants from S. flexneri 2a which repaired histidine and proline auxotropies in the Escherichia coli K-12 recipient 6. Safety and efficacy of invasive E. coil hybrid vaccines in humans have not yet been established. In the design of an effective vaccine, it is thus most crucial and important to recognize the antigenic components of the bacterial fraction or to identify the functional epitopes that are able to activate both T and IgA producing B cells. One way to approach this problem is to identify serologically a protein by immunoblotting and then cut the appropriate fraction from a nitrocellulose strip and add that to T-cell proliferation assays 7"8. Thus, it can be determined whether or not the molecule recognized by the antibody is also stimulating T cells. If one or more T cell activating antigens could be identified in shigella species, they would be obvious components to include in any hybrid vaccine. Kinetics
O'Brien, A.D. and Holmes, R.K. Shiga and Shiga-like toxins. Mierobiol. Rev. 1987, 51,206 2 Clerc, P.L., Rytar, A., Monuier, J. and Sansonetti, P.J. Plasmid mediated early killing of Encaryotic cells by Shigella flexneri as studied by infection of J 774 Microphages. Infect. Immun. 1987, 55, 521 3 Sansonetti, P.J., Rytar, A., Clerc, P., Maurelli, A.T. and Mounier, J. Multiplication of Shigella flexneri within HeLa cells: lysis of the phagocytic vacuoles and plasmid mediated contact hemolysis. Infect. Immun. 1986, 51,461 4 Hale, T.L., Morris, R.E. and Bonventre, P.F. Shigella infection of Henle,intestinal epithelial cells: role of the host cell. Infect. Immun. 1979, 24, 887 5 Mel, D., Gangarosa, E.J., Radovanovic, M.L., Arsic, B.L. and Litvinjenko, S. Studies on vaccination against bacillary dysentery 6. Protection of children by oral immunization of Streptomycin dependent Shigella strains. Bull. WHO 1971, 45, 457 6 Formal, S.B., Hale, T.L., Kapfer, C., Cogan, J.P., Snoy, P.J., Chung, R., Wingfield, M.E., Elisberg, B.L. and Baron, L.S. Oral vaccination of monkeys with an invasive Escherichia coil K-12 hybrid expressing Shigella flexneri 2a somatic antigen. Infect./mmun. 1984, 46, 465 7 Abon-Zeid, C., Filley, E, Steele, J. and Rook, G.A.W. A simple new method for using antigens separated by polyscrylamide gel elsctrophoresis to stimulate lymphocytes in-vitro by converting lines cut from Western blots into antigen-bearing particles. J. Immunol. Methods 1987, 98, 5 8 Young, D.B. and Lamb, J.R. T-lymphocytes respond to solid-phase antigen: a novel approach to molecular analysis of cellular immunity. Immunology 1986, 5~, 167
A.K. Sinha and S.C. P a l National Institute of Cholera and Enteric Diseases, P-33, CIT Road, Scheme X M , Beliaghata, Calcutta-700 010, India
Rabies antibody profile among pregnant females administered therapeutic postexposure vaccine during pregnancy, their neonates and infants Administration of purified Vero cell rabies vaccine to 21 pregnant females with laboratory confirmed rabies, during all three trimesters of pregnancy at the Queen Saovabha Memorial Institute in Bangkok, Thailand, has been free of all adverse reactions attributable to vaccine. Except for one instance of abortion during the first trimester and delivery of
premature infants in two cases, the pregnancy outcome in the rest of the vaccinated females has been uneventful. Even during the follow-up period of one year, all the 20 infants born to rabies-immunized mothers have remained healthy with no deviation from their expected growth pattern and development t. Nevertheless, any extrapolation
Book Reviews of encouraging trends from these 20 mother- infant pairs in Thailand, towards an innocuity of rabies vaccine during pregnancy universally, would be rather pre-emptive. Information about the post-vaccination immune response of mothers, passive antibody transfer to the fetus and persistence of maternally acquired antibody during infancy, is lacking. A qualitative and quantitative evaluation of immune response could be worked out by assaying both T- and B-cell dependent responses on blood samples drawn at varying stages in pregnancy, paired materno-fetal blood at delivery and frequent blood sampling during infancy. Serum aliquots from 21 pregnant females or 20 infants, if still available, could be screened for IgM and IgG rabies antibody. Any maternally acquired rabies antibody during infancy could be expected to alter the host response to rabies virus. Serological profiles on serum aliquots during early infancy could assist in determination of the half-life of rabies specific maternally acquired immunoglublins. Any pre-exposure rabies antibody in an individual domiciled in hyperendemic areas could, in the event of rabies exposure and vaccination, produce a significantly higher antibody response. In
Cairo, Egypt, human diploid rabies cell vaccine was offered to five cases of a rabid puppy bite and 17 cases of licking. In ten patients, the pre-exposure rabies antibody ranged from 0.1-3.1 IUm1-1, mean 1.0 IU m l - 1. Following vaccination, the mean day-24 antibody titre in ten patients with a pre-exposure antibody was 39.2 IU m l - t, as against 20.6 IU m l - 1 in seven patients without any pre-exposure antibody 2. No opportunity should be missed to determine if the maternally acquired antibody in 20 Thai infants or pre-school age children 1 would indeed enhance immune response to purified Vero cell rabies vaccine in the event of their chance exposure to rabies virus. Such novel data could be valuable in alterations/modifications of rabies immunization schedules for children. Basically, children and infants are friendly towards animals and are also unable to defend themselves, and indeed the incidence of rabies is highest among children 3. They are not spared even in instances of mass biting by rabid animals in small population sites. The concordance or discordance for rabies antibody titres in 20 paired cordmaternal blood samples t can be worked out by calculating the expression; cord blood titre/maternal blood titre. Any pair with values ranging between 0.5-2 would
imply concordance, while values ~/4.0 would mean discordance. Wide interregional variations in materno-fetal concordance or discordance have been known with three poliovirus serotypes and explained by variation in climatic, nutritional and physical factors 4. Similar baseline data for rabies from different hyperendemic areas would be ideal and could help in predicting if an observed low titre in a neonate could imply an insufficient titre in the mother. S.C. Arya Centre for Logistical Research and Innovation, M-122, Greater Kailash, Part 2, New Delhi 110048, India
References 1 2
3 4
Chutivongse, S. and Wilde, H. Postexposure rabies vaccination during pregnancy: experience with 21 patients. Vaccine 1989, 7, 546-548 Kilpatrick, ME., Botros, B.A.M., Bucci, T.J. and Ross, S.A. Value of pre-exposure rabies human diploid ceil vaccine for individuals living in areas hyperendemic for rabies. Vaccine 1987, 5, 260 Grossman, M. Pediatrics (Ed. Rudolph, A.M. and Hoffman, J.I.E.) Appleton and Lange, Norwalk, Connecticut, 1987, pp. 603-606 Rodriguez-Burgos, A., Bada, J.L., Fernan dezCalvo, J.L. and de Artola, V.M. Seroepidemiology of the poliovirus in Monrovia (Liberia). Trans. R. Soc. Trop. Med. Hyg. 1977, 71,118-126
Book Reviews The Orthopoxviruses F. Fenner, R. Wittek and K. R. Dumbell, Academic Press Inc., New York, 1989, p 432 $60, ISBN 9-122 530454
This is a very attractive book. It reviews, in a remarkably comprehensive way, the biology of orthopoxiviruses ranging from the molecular characteristics of their genomes to the unique features of pathogenesis of different virus-host combinations. It is fortunate that three scientists with such an unique accumulated competence in the field have undertaken the task of putting this book together. At least by one of the authors, Dr F. Fenner, who is a co-author of the World Health Organization--sponsored almost 1500 page volume on 'Smallpox and its eradication', it must have been asked what the motivation for another volume on orthopoxviruses might be. However, as clearly stated by the authors the integrated knowledge accumulated in the present book was never previously brought together. The book is composed of 12 chapters beginning with an overview orchestrating the distribution of topics in subsequent
chapters and finishing with a timely chapter on vaccinia vectorology. The writing is lucid but still amalgamates a large amount of diverse information. It is tempting to provide remarks to each separate chapter. However, I restrict myself to some select comments and leave the rest to be discovered by individual readers. Obviously for someone peripherally involved in trying to give proper focus on the important biological role of extracellular enveloped infectious particles it is a major satisfaction to note that proper credit has been given to this kind of particle, the true virion of poxviruses. Thus Dr Payne's and his collaborators work is appropriately cited, with inherent consequences for discussions on structural-functional relationships of different virus components, morphogenesis and pathogenesis. Eradication of smallpox is succinctly covered in chapter 5 and 11 which also include an exhaustive discussion on the enigmatic origin of vac-
cinia virus. Among the chapters on individual poxviruses one can find an in depth analysis of infection of man with monkeypoxvirus. Interesting information is also presented on some newly discovered poxviruses such as racoon viruses. Such viruses are potential candidates for vaccinia vector immunization against orthopoxvirus infections of importance in animals. This book may be somewhat too specialized for use in a general virology course, but it provides excellent material for any electives or seminars within this subject. The book is warmly recommended to scientists and physicians interested in the molecular basis of infectious pathogenesis. The highly interesting and unique poxvirus family represented by comparatively complex cytoplasmic DNA viruses with a high degree of selfsufficiency deserves attention also in the future despite the magnificant achievement of eradication of smallpox. The potential use of poxviruses as vectors and their role in zoonotic or veterinary contexts motivates the retention of alterness on accumulation of future knowledge on their biology. E. Norrby Karolinska Institutet Stockholm, Sweden
Vaccine, Vol. 8, August 1990 411
Pittman, M. Neurotoxicity of Bordetalla pertussis. Neurotoxioology 1986, 7, 53 13 Workshop on Acellular Pertussls Vaccine Sponsored by the Intaragency Group to Monitor Vaccine Development, Production and Usage, US Department of Health and Human Services and US Public Health Service (Transcripts available from Dr C.R. Manclark, Center of Biologics Evaluation and Research, 8800 Rockville Pike, Bethesda, MD 20892, USA) 1986, pp. 1-301 14 Robinson, A. and Ashworth, L.A.E. Acellular and defined-component vaccines against pertussis. In: Pathogenesis and Immunity in Pertussis (Eds Wardlaw, A.C. and Patton, R.) John Wiley, Chichester, 1988, pp. 399-417
Gupta, R.K. Development of an improved pertussis vaccine. Ph.D. Thesis Himachal Pradesh University, Shimla, 1987
R.K. G u p t a Visiting Fellow Laboratory of Developmental and Molecular Immunity, NICHD, National Institutes of Health, Bethesda, MD 20892, USA
of proliferative response of T cell activating antigen after exposing bacterial fractions to peripheral blood mononuclear cells (PBMC) from individuals who have recently been infected with shigella is more relevant in the design of the subunit of the vaccine. This new avenue of the above research could also shed important light on protection from shigella infection.
References 1
New approach to develop a vaccine design against shigellosis The development of a vaccine against shigellosis caused by Shioella dysenteriae type 1 is a global intervention strategy for three important reasons- the epidemic potential of the organism, its high virulence and its remarkable ability quickly to acquire resistance to almost all antimicrobial agents. In addition, vaccines against the more common species Shioella sonnei and Shioella flexneri are also required. Immunization by the parenteral route using killed vaccines has been ineffective since they are T cell independent and do not evoke secondary responses on repeated vaccination. F o r more than three decades, several groups of workers ~ have worked on the pathophysiology of the disease and the role of toxin produced by S. dysenteriae 1. So far, available data are not convincing enough to confirm the role of shiga-toxin in the pathogenesis of shigellosis. There are as yet many missing links which need to be explored before rational development of immunoprophylaxis is undertaken. In shigellosis, multi-host factors are responsible for invasion and colonization. Recovery from the disease would primarily depend on development of effective deeper tissue immunity and the role of cellular immunity of the host may be a critical factor in protection against shigellosis, as it is an intracellular pathogen during most of its life cycle. In 1971, streptomycin-dependent attenuated vaccines were widely tested in Yugoslavia 5 and conferred a significant degree of protection in field studies, but these vaccines were somewhat unstable. However, a live vaccine strain can be developed by genetically modifying the pathogen itself so that it loses its virulence but retains immunogenicity. This can be done by identifying the protective antigens of the pathogen and transferring these to a harmless carrier bacterium. Both conventional genetics and recombinant DNA technology can be used to achieve these goals. However, no successful vaccine
410 Vaccine, Vol. 8, August 1990
strain has yet been developed. A carrier based vaccine strain was constructed by isolation of tr~nsconjugants from S. flexneri 2a which repaired histidine and proline auxotropies in the Escherichia coli K-12 recipient 6. Safety and efficacy of invasive E. coil hybrid vaccines in humans have not yet been established. In the design of an effective vaccine, it is thus most crucial and important to recognize the antigenic components of the bacterial fraction or to identify the functional epitopes that are able to activate both T and IgA producing B cells. One way to approach this problem is to identify serologically a protein by immunoblotting and then cut the appropriate fraction from a nitrocellulose strip and add that to T-cell proliferation assays 7"8. Thus, it can be determined whether or not the molecule recognized by the antibody is also stimulating T cells. If one or more T cell activating antigens could be identified in shigella species, they would be obvious components to include in any hybrid vaccine. Kinetics
O'Brien, A.D. and Holmes, R.K. Shiga and Shiga-like toxins. Mierobiol. Rev. 1987, 51,206 2 Clerc, P.L., Rytar, A., Monuier, J. and Sansonetti, P.J. Plasmid mediated early killing of Encaryotic cells by Shigella flexneri as studied by infection of J 774 Microphages. Infect. Immun. 1987, 55, 521 3 Sansonetti, P.J., Rytar, A., Clerc, P., Maurelli, A.T. and Mounier, J. Multiplication of Shigella flexneri within HeLa cells: lysis of the phagocytic vacuoles and plasmid mediated contact hemolysis. Infect. Immun. 1986, 51,461 4 Hale, T.L., Morris, R.E. and Bonventre, P.F. Shigella infection of Henle,intestinal epithelial cells: role of the host cell. Infect. Immun. 1979, 24, 887 5 Mel, D., Gangarosa, E.J., Radovanovic, M.L., Arsic, B.L. and Litvinjenko, S. Studies on vaccination against bacillary dysentery 6. Protection of children by oral immunization of Streptomycin dependent Shigella strains. Bull. WHO 1971, 45, 457 6 Formal, S.B., Hale, T.L., Kapfer, C., Cogan, J.P., Snoy, P.J., Chung, R., Wingfield, M.E., Elisberg, B.L. and Baron, L.S. Oral vaccination of monkeys with an invasive Escherichia coil K-12 hybrid expressing Shigella flexneri 2a somatic antigen. Infect./mmun. 1984, 46, 465 7 Abon-Zeid, C., Filley, E, Steele, J. and Rook, G.A.W. A simple new method for using antigens separated by polyscrylamide gel elsctrophoresis to stimulate lymphocytes in-vitro by converting lines cut from Western blots into antigen-bearing particles. J. Immunol. Methods 1987, 98, 5 8 Young, D.B. and Lamb, J.R. T-lymphocytes respond to solid-phase antigen: a novel approach to molecular analysis of cellular immunity. Immunology 1986, 5~, 167
A.K. Sinha and S.C. P a l National Institute of Cholera and Enteric Diseases, P-33, CIT Road, Scheme X M , Beliaghata, Calcutta-700 010, India
Rabies antibody profile among pregnant females administered therapeutic postexposure vaccine during pregnancy, their neonates and infants Administration of purified Vero cell rabies vaccine to 21 pregnant females with laboratory confirmed rabies, during all three trimesters of pregnancy at the Queen Saovabha Memorial Institute in Bangkok, Thailand, has been free of all adverse reactions attributable to vaccine. Except for one instance of abortion during the first trimester and delivery of
premature infants in two cases, the pregnancy outcome in the rest of the vaccinated females has been uneventful. Even during the follow-up period of one year, all the 20 infants born to rabies-immunized mothers have remained healthy with no deviation from their expected growth pattern and development t. Nevertheless, any extrapolation
Book Reviews of encouraging trends from these 20 mother- infant pairs in Thailand, towards an innocuity of rabies vaccine during pregnancy universally, would be rather pre-emptive. Information about the post-vaccination immune response of mothers, passive antibody transfer to the fetus and persistence of maternally acquired antibody during infancy, is lacking. A qualitative and quantitative evaluation of immune response could be worked out by assaying both T- and B-cell dependent responses on blood samples drawn at varying stages in pregnancy, paired materno-fetal blood at delivery and frequent blood sampling during infancy. Serum aliquots from 21 pregnant females or 20 infants, if still available, could be screened for IgM and IgG rabies antibody. Any maternally acquired rabies antibody during infancy could be expected to alter the host response to rabies virus. Serological profiles on serum aliquots during early infancy could assist in determination of the half-life of rabies specific maternally acquired immunoglublins. Any pre-exposure rabies antibody in an individual domiciled in hyperendemic areas could, in the event of rabies exposure and vaccination, produce a significantly higher antibody response. In
Cairo, Egypt, human diploid rabies cell vaccine was offered to five cases of a rabid puppy bite and 17 cases of licking. In ten patients, the pre-exposure rabies antibody ranged from 0.1-3.1 IUm1-1, mean 1.0 IU m l - 1. Following vaccination, the mean day-24 antibody titre in ten patients with a pre-exposure antibody was 39.2 IU m l - t, as against 20.6 IU m l - 1 in seven patients without any pre-exposure antibody 2. No opportunity should be missed to determine if the maternally acquired antibody in 20 Thai infants or pre-school age children 1 would indeed enhance immune response to purified Vero cell rabies vaccine in the event of their chance exposure to rabies virus. Such novel data could be valuable in alterations/modifications of rabies immunization schedules for children. Basically, children and infants are friendly towards animals and are also unable to defend themselves, and indeed the incidence of rabies is highest among children 3. They are not spared even in instances of mass biting by rabid animals in small population sites. The concordance or discordance for rabies antibody titres in 20 paired cordmaternal blood samples t can be worked out by calculating the expression; cord blood titre/maternal blood titre. Any pair with values ranging between 0.5-2 would
imply concordance, while values ~/4.0 would mean discordance. Wide interregional variations in materno-fetal concordance or discordance have been known with three poliovirus serotypes and explained by variation in climatic, nutritional and physical factors 4. Similar baseline data for rabies from different hyperendemic areas would be ideal and could help in predicting if an observed low titre in a neonate could imply an insufficient titre in the mother. S.C. Arya Centre for Logistical Research and Innovation, M-122, Greater Kailash, Part 2, New Delhi 110048, India
References 1 2
3 4
Chutivongse, S. and Wilde, H. Postexposure rabies vaccination during pregnancy: experience with 21 patients. Vaccine 1989, 7, 546-548 Kilpatrick, ME., Botros, B.A.M., Bucci, T.J. and Ross, S.A. Value of pre-exposure rabies human diploid ceil vaccine for individuals living in areas hyperendemic for rabies. Vaccine 1987, 5, 260 Grossman, M. Pediatrics (Ed. Rudolph, A.M. and Hoffman, J.I.E.) Appleton and Lange, Norwalk, Connecticut, 1987, pp. 603-606 Rodriguez-Burgos, A., Bada, J.L., Fernan dezCalvo, J.L. and de Artola, V.M. Seroepidemiology of the poliovirus in Monrovia (Liberia). Trans. R. Soc. Trop. Med. Hyg. 1977, 71,118-126
Book Reviews The Orthopoxviruses F. Fenner, R. Wittek and K. R. Dumbell, Academic Press Inc., New York, 1989, p 432 $60, ISBN 9-122 530454
This is a very attractive book. It reviews, in a remarkably comprehensive way, the biology of orthopoxiviruses ranging from the molecular characteristics of their genomes to the unique features of pathogenesis of different virus-host combinations. It is fortunate that three scientists with such an unique accumulated competence in the field have undertaken the task of putting this book together. At least by one of the authors, Dr F. Fenner, who is a co-author of the World Health Organization--sponsored almost 1500 page volume on 'Smallpox and its eradication', it must have been asked what the motivation for another volume on orthopoxviruses might be. However, as clearly stated by the authors the integrated knowledge accumulated in the present book was never previously brought together. The book is composed of 12 chapters beginning with an overview orchestrating the distribution of topics in subsequent
chapters and finishing with a timely chapter on vaccinia vectorology. The writing is lucid but still amalgamates a large amount of diverse information. It is tempting to provide remarks to each separate chapter. However, I restrict myself to some select comments and leave the rest to be discovered by individual readers. Obviously for someone peripherally involved in trying to give proper focus on the important biological role of extracellular enveloped infectious particles it is a major satisfaction to note that proper credit has been given to this kind of particle, the true virion of poxviruses. Thus Dr Payne's and his collaborators work is appropriately cited, with inherent consequences for discussions on structural-functional relationships of different virus components, morphogenesis and pathogenesis. Eradication of smallpox is succinctly covered in chapter 5 and 11 which also include an exhaustive discussion on the enigmatic origin of vac-
cinia virus. Among the chapters on individual poxviruses one can find an in depth analysis of infection of man with monkeypoxvirus. Interesting information is also presented on some newly discovered poxviruses such as racoon viruses. Such viruses are potential candidates for vaccinia vector immunization against orthopoxvirus infections of importance in animals. This book may be somewhat too specialized for use in a general virology course, but it provides excellent material for any electives or seminars within this subject. The book is warmly recommended to scientists and physicians interested in the molecular basis of infectious pathogenesis. The highly interesting and unique poxvirus family represented by comparatively complex cytoplasmic DNA viruses with a high degree of selfsufficiency deserves attention also in the future despite the magnificant achievement of eradication of smallpox. The potential use of poxviruses as vectors and their role in zoonotic or veterinary contexts motivates the retention of alterness on accumulation of future knowledge on their biology. E. Norrby Karolinska Institutet Stockholm, Sweden
Vaccine, Vol. 8, August 1990 411
