Jan Fohlman has completed his PhD and MD from Freiburg, Linköping, Uppsala University and has been working as a consultant in infectious diseases for >30 years, now at Dept of Research and Development Region Kronoberg, Växjö, working closely with Linnaeus Univeristy. He is a board member of 3Diva AB, a recently started vaccine development company . He has published more than 100 papers in reputed journals and has been serving as a referee for multiple journals.
Background: Attempts to conquer influenza are struggling with the complexity of hypervariability. CDC issued a warning already in December 2014 that the profile of influenza viruses currently circulating (with A/H3N2 predominating) did not match with the corresponding strain in the vaccine. The flu season 2015 was severe. There was no protection against 97 % of the virus strains, 40 % higher mortality in England, 7 % of all mortality in USA in December due to influenza and about 1000 persons succumbing to flu in Sweden this season.
Aim: This raises the question whether it is possible to construct a vaccine that gives a heterotypic protection. ISCOM H1N1 influenza vaccine protected mice against H2N2 influenza strain challeng(1). A commercial vaccine (Pandemrix®) was issued in 2010 and gave a longer lasting immunoprotection, apparently due to the use of squalene as an adjuvant. Unfortunately a strain of influenza was selected that later turned out to cause narcolepsy in predisposed individuals, esp children (3). This could not have been anticipated and not even tested beforehand, due to the rarity of the condition, even if it was increased about 3-fold.
Methods: A further development of ISCOM is now under investigation under the name of G3/DT®. A vaccine H1N1 A/California/7/2009 (H1N1pdm09) protected against a lethal challenge with antigenically distinct H1N1 A/PR8/34 in a mouse model (2). The adjuvanted vaccine gave a high level of protective antibodies. Also influenza A virus-specific CD8+ T lymphocytes were induced and seem responsible for the heterotypic response.
Conclusions: No adjuvanted influenza vaccine has so far been licensed in the US. To meet the problem of non-matching strains adjuvanted vaccines might be advantageous for protection against yearly flu infection.
Hiroko Toriniwa recieved her phD frome Faculty of Environmental Earth Science, Hokkaido University. She is Senior Researcher of Vaccine Research Laboratories, R&D Division, KITASATO DAIICHI SANKYO VACCINE CO., LTD. She have researched development of Japanese encphalitis virus vaccine. She is coauthor of the patent : Method of producing japanese encephalitis vaccine stably storable over long time and use of the vaccine with reference PCT/JP2008/073732.
We previously developed an inactivated Japanese encephalitis virus (JEV) vaccine (ccJE) using serum-free cultured Vero cells. The immunogenicity of this ccJE vaccine was enhanced by formulation with AdvaxTM, a novel polysaccharide adjuvant based on delta inulin thereby enabling JEV protection after just a single immunisation. Advax adjuvant potently stimulated humoral and cellular immunity but avoided the reactogenicity of other adjuvants. Immunisation of mice with the ccJE-Advax vaccine combination induced cross-neutralising antibodies against other Flaviviruses belonging to the JEV serocomplex, including Murray Valley encephalitis virus (MVEV) and West Nile virus (WNV). We thereby sought to identify the immune mechanism underlying this cross protection. The ccJE-Advax combination changed the balance of T cell immunity as reflected by changes in the IgG antibody isotypes. Splenocytes from mice immunized with ccJE-Advax when compared to mice immunized with ccJE antigen alone exhibited increased IFN-γand IL-17 production when stimulated with ccJE antigen, consistent with Advax adjuvant increasing Th1 and Th17 immunity. Increased antigen-specific T-cell IL-17 production and protection against JEV challenge was also seen in an IFN-γ knockout mouse model, indicating that IFN-γwas not critical to ccJE-Advax mediated protection. Thus the combination of ccJE-Advax induces broad humoral and cellular immunity against JEV, translating into single-dose protection. This broader immunity obtained through use of Advax adjuvant in the vaccine enables enhnhanced cross-neutralising antibody and T-cell responses against not just JEV but also other JEV serocomplex flaviviruses including WNV and MVEV, with enhanced antigen-specific Th1 and Th17 immune responses.