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.

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.

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.

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.

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.

Antigenic and molecular properties of type 3 poliovirus responsible for an outbreak of poliomyelitis in a vaccinated population.

Virus isolated from an outbreak of poliomyelitis in Finland has been examined serologically and at the molecular level. The causative agent was an antigenically unusual strain of type 3 poliovirus, which was unrelated to the strains used to manufacture either live or killed poliovaccines. It is likely that the antigenic properties of the virus played a part in establishing a limited outbreak of poliomyelitis in a vaccinated population.

WHO collaborative study on the use of monoclonal antibodies for the intratypic differentiation of poliovirus strains.

An international collaborative study was carried out to identify monoclonal antibodies that could reliably discriminate between wild polioviruses and strains derived from Sabin vaccine viruses. For poliovirus types 2 and 3, monoclonal antibodies were identified that reacted specifically with type 2 or type 3 strains which gave T1-oligonucleotide maps similar to or indistinguishable from that of Sabin vaccine virus, thus indicating their vaccine origin. These monoclonal antibodies failed to react with strains which gave T1 maps unrelated to that of Sabin vaccine virus.

Induction by synthetic peptides of broadly reactive, type-specific neutralizing antibody to poliovirus type 3.

A region of virus capsid protein VP1 located 89-100 amino acids from the N-terminus has been proposed to comprise a major antigenic site involved in the neutralization of poliovirus type 3. Synthetic peptides 10-18 amino acids in length, containing all or part of this sequence, were tested for their ability to induce antiviral antibodies. Rabbits, but not guinea pigs or mice, immunized with the most active peptide, developed hightitered, type-specific, neutralizing antibodies for a wide range of poliovirus type 3 strains.

The standardization of infectivity titrations of poliovaccines--a WHO collaborative study.

The reproducibility of a method for infectivity titrations of live poliovaccines using microtitre plates was investigated in a WHO collaborative study involving eight laboratories. The large variation (up to 100-fold) in estimates of infectivity observed between laboratories using their local methods of assay was reduced to no more than fourfold when a common method was used. However, expressing infectivities relative to those of the monovalent reference viruses improved the agreement between the laboratories irrespective of the titration method employed.

Antigenic characterization of poliovirus type 3 using monoclonal antibodies.

Hybridoma cell lines secreting monoclonal antibodies to type 3 poliovirus were prepared, and their reactivity with infectious virus (D antigen), empty particles (C antigen), and isolated virion capsid proteins ( VPs ) were examined. Eight antibodies reacted with epitopes common to D and C antigens, and all of these possessed high titers of neutralizing activity. However, only 12 of 19 antibodies that reacted exclusively with D antigen neutralized virus infectivity, and some of these reacted only with strains of virus with T1-oligonucleotide maps identical or similar to that of Sabin vaccine polio virus.

Neutralization epitopes on poliovirus type 3 particles: an analysis using monoclonal antibodies.

Monoclonal antibodies to poliovirus type 3 secreted by 51 hybridoma cell clones have been characterized in terms of (i) virus-neutralizing properties, (ii) reactivity in antigen-blocking tests with infectious, 155S ('D' antigen) and empty 80S ('C' antigen) poliovirus particles and (iii) reactivity in immunoblot tests with the isolated protein components of the poliovirus capsid. The antibodies could be separated into three groups on the basis of their reactivities with 'D' and 'C' antigens. All antibodies that reacted with both 'D' and 'C' antigen had potent neutralizing activity.