Immunogenicity of oral poliovirus vaccine administered in mass campaigns versus routine immunization programmes.

Reported are the results of a study to investigate the immunogenicity of oral poliovirus vaccine (OPV) when administered in mass campaigns compared with that following routine immunization programmes. For this purpose, paired sera were collected from a cohort of children before and after a mass vaccination with OPV in Morocco in 1987. Serum samples and information on vaccination status and other confounding factors that could influence antibody responses to OPV were collected. Neutralizing antibody titres to poliovirus types 1, 2 and 3 were determined using a standardized assay. OPV doses administered exclusively during the mass campaign were consistently associated with higher type-specific seroprevalence rates than the same number of doses administered in the routine programme. These findings could not be attributed to differences in confounding factors. Enhanced secondary spread of vaccine virus may have occurred but could not be demonstrated because of limitations in the study design. Mass campaigns appear to be highly effective in raising the dose-related poliovirus type-specific immunity of the population above that achieved by the routine immunization programme. Our findings support the continued use of mass campaigns as an adjunct to routine programmes in order to both enhance and catalyse current efforts to achieve the global eradication of poliomyelitis by the year 2000.

PIP: Reported are the results of a study to investigate the immunogenicity of oral poliovirus vaccine (OPV) when administered in mass campaigns compared with that following routine immunization programs. For this purpose, paired sera were collected from a cohort of children before and after a mass vaccination with OPV in Morocco in 1987. Serum samples and information on vaccination status and other confounding factors that could influence antibody responses to OPV were collected. Neutralizing antibody titers to poliovirus types 1, 2, and 3 were determined using a standardized assay. OPV doses administered exclusively during the mass campaign were consistently associated with higher type-specific seroprevalence rates than the same number of doses administered in the routine program. These findings could not be attributed to differences in confounding factors. Enhanced secondary spread of vaccine virus may have occurred but could not be demonstrated because of limitations in the study design. Mass campaigns appear to be highly effective in raising the dose-related poliovirus type-specific immunity of the population above that achieved by the routine immunization program. These findings support the continued use of mass campaigns as an adjunct to routine programs in order to both enhance and catalyze current efforts to achieve the global eradication of poliomyelitis by the year 2000. (author's)

On the role of the World Health Organization in the development of Sabin vaccines.

The World Health Organization has played a major part in the development, surveillance and distribution of attenuated poliovirus vaccines. At a time when most of the United States' efforts concerned the introduction of Salk-type vaccines, WHO initiated studies that set standards and permitted the large scale trials of Sabin and other attenuated vaccines. Independent expert review validated studies in countries such as the U.S.S.R. which helped lead to the adoption of Sabin vaccines for worldwide usage. Surveillance by WHO Collaborative Centres established the safety of Sabin vaccines and identified issues of reversion primarily concerning type 3 viruses, initiating studies which have elucidated the molecular mechanism of reversion. Efforts by the Biological Unit of the World Health Organization have ensured worldwide acceptable standards to control the safety and manufacture of vaccines. Revision of neurovirulence test methods has ensured adequate safety testing of vaccine lots, reduced the costs of such studies and the numbers of primates needed, important ethical and conservation issues. Finally, the World Health Organization has played a major part in the worldwide supply of vaccines at affordable prices and has been the repository of, and had the exclusive license, to Sabin vaccines since 1972.

Availability of vaccines of an assured quality.

In establishing standards of quality for vaccines used in vaccination programmes, it is necessary to protect the recipients without demanding unnecessarily high specifications and standards of purity. Such standards reduce profitability, jeopardizing further vaccine supplies and future research, and also diminish the probability of vaccine manufacture outside the industrialized countries. Funds will be needed to encourage research and local manufacture, and internationally accepted procedures of quality assurance must be established.

Durability of immunity to diphtheria, tetanus and poliomyelitis after a three dose immunization schedule completed in the first eight months of life.

Blood samples were obtained from school entrants whose primary immunization schedule had consisted of three doses of DT or DTP vaccine and three doses of OPV all given before the age of 8 months. The sera were separated and assayed for diphtheria antitoxin, tetanus antitoxin and antibodies to the three serotypes of poliovirus. The results of the assays showed that the abbreviated three dose schedule induced satisfactory immunity to all five infections until school entry and that a reinforcing dose at 18 months was unnecessary.

The temperature sensitivity of the Sabin type 3 vaccine strain of poliovirus: molecular and structural effects of a mutation in the capsid protein VP3.

The growth of the Sabin strain of type 3 poliovirus is reduced at high temperatures compared to that of its virulent precursor strain Leon. Recombinant viruses have been generated from infectious cDNA clones and demonstrate that the temperature-sensitive (ts) phenotype is mainly attributable to a difference in residue 91 of the virion protein VP3. Examination of non-ts mutants derived in vitro or in vivo reveals the existence of second site mutations some of which are clearly able to suppress the ts phenotype. The location of residue 91 of VP3, and of a number of candidate suppressor mutations, in the atomic structure of the virion suggests that the ts phenotype may result in destabilization of the particle and that the suppressors may function by stabilizing specific interfaces. It is not yet clear whether the ts phenotype is expressed at the level of the particle or in the form of defects in assembly or uncoating of the virion, or all three.

Genetic basis of attenuation of the Sabin type 3 oral poliovirus vaccine.

The poliovirus type 3 Sabin oral poliovirus vaccine strain P3/Leon/12a1b differs in nucleotide sequence from its neurovirulent progenitor P3/Leon/37 by just 10 point mutations. The contribution of each mutation to the attenuation phenotype of the vaccine strain was determined by the construction of a series of recombinant viruses from infectious cDNA clones. The neurovirulence testing of recombinant viruses indicated that the attenuation phenotype is determined by just two point mutations: a C to U in the noncoding region at position 472 and a C to U at nucleotide 2034 which results in a serine-to-phenylalanine amino acid substitution in the structural protein VP3.

Studies on the attenuation of the Sabin type 3 oral polio vaccine.

The genetic basis of attenuation of the poliovirus type 3 vaccine strain P3/Leon 12a1b has been investigated by comparing the nucleotide sequence of this strain with that of its neurovirulent progenitor P3/Leon/37 and by constructing recombinants between these two viruses using infectious cDNAs. Preliminary results suggest that attenuation is caused by just two point mutations, one occurring in the 5' non-coding region and the other causing an amino acid change in coat protein VP3.

Antibody state to poliovirus in first year university students, 1984.

Circulating antibodies to poliovirus were estimated in a group of 300 British and 84 foreign first year students who registered at the health centre of Nottingham University in 1984. Detectable antibodies to all three poliovirus serotypes were found in 212 (71%) of the British students but in only 47 (56%) of those from abroad. Most of the British students (280; 93%) had been born in 1965 or 1966, when uptake of poliomyelitis vaccine was declining. Immunisation histories showed that 10 British and 29 foreign students (3% and 35%) had no record of any immunisation; only five British and two foreign students, however, were negative for all three poliovirus serotypes. These findings provide evidence that a high proportion of British born people aged 18-29 have adequate circulating poliovirus antibodies despite incomplete immunisation schedules. Though this is reassuring, the absence of antibodies in some students and the lack of previous immunisation against poliomyelitis in 39 suggest that reinforcing doses of vaccine at the time of leaving school or beginning further education are still warranted, particularly for students from other countries. The findings also emphasise the need for accurate immunisation records.

Conservation in vivo of protease cleavage sites in antigenic sites of poliovirus.

Polioviruses possess three major antigenic sites which have been located chemically and structurally on the particle. One of these sites, designated site 1, is strongly immunodominant for serotype 3, but highly immunorecessive for type 1. We report that monoclonal antibodies directed against site 1 of type 1 poliovirus may be isolated by an altered route of immunization of the donor mice. Site 1 is shown to be highly variable for type 1, but highly conserved for type 3 poliovirus, although the converse would be predicted from their immunodominance. The evidence presented suggests that the antigenic conservation is associated with a strong selective pressure for a proteolytic cleavage site within site 1 of type 3. As proteolytic cleavage results in the loss of the antigenicity of site 1 the presence of the cleavage site in a virus replicating in the gut in the presence of proteases would protect the virus from neutralizing antibodies directed against uncleaved site 1. The conservation of the site in type 3 is thus consistent with the view that site 1 is a significant target of a human as well as a murine immune response against type 3.