Preparation of vaccines against H5N1 influenza.

In response to the pandemic warning provided by the highly pathogenic H5N1 influenza virus infections in Hong Kong, there were world-wide attempts to develop vaccines. Three strategies were followed and although each was associated with some success, there were also some problems. Pre-clinical vaccine efficacy results are presented from one such strategy, that of using an apathogenic H5N3 avian strain for vaccine production.

The influence of the host cell on standardisation of influenza vaccine potency.

Conventional influenza vaccines are standardised using the single-radial-immunodiffusion (SRD) test where reagents are produced from egg-grown viruses. It is important to ensure homology between SRD antigen reagents and test vaccines. There was concern that cell-grown vaccines may differ antigenically from corresponding egg-grown vaccines, which may in turn affect vaccine standardisation. In an examination of five cell-grown vaccines from two companies, only one vaccine was affected by the specificity of the SRD test. Options for standardisation of cell-grown vaccines are considered and recommendations are made for further studies.

Antigenicity and immunogenicity of experimental equine influenza ISCOM vaccines.

A comparison of the antigenicity and immunogenicity of ISCOM vaccines prepared from equine influenza viruses H3N8 and H7N7 was made with inactivated whole-virus vaccines containing equivalent amounts of virus haemagglutinin. ISCOMs stimulated superior antibody responses in terms of both amount and duration. As with conventional whole-virus vaccines, the levels of antibody to virus haemagglutinin induced by ISCOMs correlated with protection.

High growth reassortant influenza vaccine viruses: new approaches to their control.

When a new strain of an influenza virus is required to be incorporated into influenza vaccine, attempts are made to recombine such strains with laboratory adapted viruses, which will grow to high titre in order to improve the yield of the vaccine strain. It is important that such high growth reassortant vaccine strains are not contaminated with genes coding for the antigenic determinants of the high growth laboratory strain. We describe the characterization of two recent high growth reassortants and the application of the polymerase chain reaction to ensure their genetic identity and purity.

Influenza A (H1N1) vaccine efficacy in animal models is influenced by two amino acid substitutions in the hemagglutinin molecule.

The immunogenicity and protective efficacy of formalin-inactivated vaccines prepared from influenza A (H1N1) viruses grown in MDCK cells and in eggs was compared in animal models. The A/Chr/157/83 virus grown in MDCK cells (157M) differed by two amino acid substitutions in the HA molecule from the corresponding virus grown in eggs (157E) and the two viruses could be distinguished antigenically by monoclonal and polyclonal antibodies. Following two intramuscular injections of vaccine in ferrets, guinea pigs, and hamsters, both vaccines were equally immunogenic when antibody was analyzed by hemagglutination inhibition using homologous virus. However, single radial hemolysis analysis following antibody cross-adsorption showed that antibody stimulated by 157E vaccine was exclusively strain specific whereas that produced by the 157M vaccine was more broadly reactive. When immunized hamsters were challenged with virus cultivated on mammalian (MDCK) cells, the homologous vaccine induced a higher degree of protection than the corresponding egg-grown vaccine.

Sequential infection or immunization of ferrets with a series of influenza A (H3N2) strains (report to the Medical Research Council's Sub-Committee on influenza Vaccines (CDVIP/IV)).

Previous studies of boys at Christ's Hospital school have indicated that annual immunization with influenza virus vaccines did not significantly reduce the total incidence of influenza infection compared to unimmunized subjects. In view of the implications of this result, a similar study was conducted in ferrets to clarify these findings. Groups of ferrets were immunized or infected with a series of influenza A (H3N2) viruses over an 18-month period, and the immunity to subsequent live virus challenge was measured after each virus or vaccine exposure. The results indicated that live virus infection gave a more solid immunity than immunization with inactivated vaccine; and the serum haemagglutination-inhibiting antibody response was greater following immunization than following infection. In addition, differences in immunity could not be explained by measurements of cross-reacting and specific antibody, since the incidence of these antibodies was similar in both infected and immunized animals. The results do not suggest an explanation for the different levels of immunity induced following infection or immunization or the results obtained from the Christ's Hospital study. However, the relative contribution of various immune responses to virus or virus antigen is discussed, and it is suggested that the difference in immunity may lie in the ability of live virus infection to stimulate local antibody.