Long-Lasting Heterologous Antibody Responses After Sequential Vaccination With A/Indonesia/5/2005 And A/Vietnam/1203/2004 Pre-Pandemic Influenza A(H5n1) Virus Vaccines

Background: Avian influenza A(H5N1) viruses have caused sporadic infections in humans and thus they pose a significant global health threat. Among symptomatic patients the case fatality rate has been ca. 50%. H5N1 viruses exist in multiple clades and subclades and several candidate vaccines have been developed to prevent A(H5N1) infection as a principal measure for preventing the disease.Methods: Serum antibodies against various influenza A(H5N1) Glade viruses were measured in adults by ELISA-based microneutralization and haemagglutination inhibition tests before and after vaccination with two different A(H5N1) vaccines in 2009 and 2011.Results: Two doses of AS03-adjuvanted A/Indonesia/5/2005 vaccine induced good homologous but poor heterologous neutralizing antibody responses against different Glade viruses. However, non-adjuvanted A/Vietnam/1203/2004 booster vaccination in 2011 induced very strong and long-lasting homologous and heterologous antibody responses while homologous response remained weak in naive subjects.Conclusions: Sequential vaccination with two different A(H5N1) pre-pandemic vaccines induced long-lasting high level cross-Glade immunity against influenza A(H5N1) strains, thus supporting a prime-boost vaccination strategy in pandemic preparedness plans. (C) 2020 The Author(s). Published by Elsevier Ltd.