Bert E. Johansson

The total influenza vaccine failure of 1947 revisited: Major intrasubtypic antigenic change can explain failure of vaccine in a post-World War II epidemic

Although vaccine-induced immunity to influenza A virus is continually challenged by progressively selected mutations in the viruss major antigens (antigenic drift), virus strains within a subtype (e.g., H1N1) are antigenically cross-reactive. Although cross-immunity diminishes as further mutations accumulate, necessitating frequent changes in vaccine strains, older vaccines are usually partially protective. The post-World War II epidemic of 1947 is notable for the total failure of a vaccine previously effective in the 1943–44 and 1944–45 seasons. We have combined extensive antigenic characterization of the hemagglutinin and neuraminidase antigens of the 1943 and 1947 viruses with analysis of their nucleotide and amino acid sequences and have found marked antigenic and amino acid differences in viruses of the two years. Furthermore, in a mouse model, vaccination with the 1943 vaccine had no effect on infection with the 1947 strain. These findings are important, because complete lack of cross-immunogenicity has been found previously only with antigenic shift, in which antigenically novel antigens have been captured by reassortment of human and animal strains, sometimes leading to pandemics. Although the 1947 epidemic lacked the usual hallmarks of pandemic disease, including an extensive increase in mortality, it warns of the possibility that extreme intrasubtypic antigenic variation (if coupled with an increase in disease severity) could produce pandemic disease without the introduction of animal virus antigens.

Identification of PR8 M1 protein in influenza virus high-yield reassortants by M1-specific monoclonal antibodies

A panel of monoclonal antibodies to the M1 protein of A/PR8/34 (H1N1) (PR8) influenza A virus was found to distinguish in ELISA high-yielding reassortant viruses derived from reassortment of PR8 and X-31 (H3N2) viruses with recently prevalent field strains of H1N1 or H3N2 subtype. These findings are concordant with results of genotyping that demonstrated the presence of PR8 RNA 7 or M1 protein in high-yield reassortants by RNA or protein PAGE. All high-yield vaccine candidate reassortants Application of the M1 monoclonal antibody panel facilitates the isolation of high-yield vaccine candidate reassortants bearing the PR8 M1 gene, and should aid in epidemiologic strain tracking as well.

Recombinant Influenza B virus HA and NA antigens administered in equivalent amounts are immunogenically equivalent and induce equivalent homotypic and broader heterovariant protection in mice than conventional and live influenza vaccines

Influenza B virus is an important cause of acute upper respiratory disease in humans. Vaccination is the primary method of control of influenza related disease, yet vaccine methodology and production technology have not changed in over 40 years. In this study, we compare the efficacy of recombinant baculovirus produced protein based neuraminidase containing influenza B vaccines with conventional inactivated influenza vaccine (CIV) and live-attenuated influenza vaccine (LAIV) in a murine model. All HA containing vaccines stimulated antibody and protected against an infectious challenge with homotypic virus (B/Harbin/7/94), only recombinant protein based (rHA+rNA and rNA) vaccines containing immunogenic amounts of influenza neuraminidase (NA) protected against challenge with a significantly antigenically different heterovariant virus (B/Beijing/243/1997), as measured by a reduction in mean pulmonary virus titers. This report demonstrates with influenza B virus, in a side-by-side comparison with CIV and LAIV in a murine model system the superiority of vaccines containing immunogenic NA over currently approved CIV and LAIV vaccines.

Programmed Antigenic Stimulation — A New Approach to Influenza Vaccination

Although much is currently written about “new vaccines” and “new approaches to immunization” most contemporary approaches represent technologic developments in the synthesis or presentation of antigens rather than departure from the strategies of the past. The old categories of live and inactivated vaccines can readily accommodate present day recombinant (replicating) viruses (live) or “subunit” or oligopeptide vaccines, perhaps better characterized as non-replicating antigens. The primary and hallowed objective of most vaccines has been the prevention of disease by the prevention of infection. Exceptions are such vaccines as rabies or hepatitis B vaccine which may be given post-exposure and with which suppression of infection already acquired is the only possible objective.

Mouse Models of Influenza

Influenza is an enveloped, segmented negative sense RNA virus capable of infecting epithelial cells lining the human respiratory tract. Influenza A and B are important causes of disease in humans. Transmitted via aerosol, the virus possesses two major surface, hemagglutinin (HA) and neuraminidase (NA). HA has binding specificity for sialic acid, and allows viral attachment and entry into the cell. NA cleaves sialic acid residues off glycoproteins or mucoproteins, which aids new progenitor virions in eluting from the cell. The primary method of reducing influenza disease burden has been through vaccination.