Inactivated influenza virus vaccines: the future of TIV and QIV

Influenza viruses continue to be a major public health concern, despite the availability of vaccines. Currently licensed influenza vaccines aim at the induction of antibodies that target hemagglutinin, the major antigenic determinant on the surface of influenza virions that is responsible for attachment of the virus to the host cell that is to be infected. Currently licensed influenza vaccines come as inactivated or live attenuated influenza vaccines and are trivalent or quadrivalent as they contain antigens of two influenza A and one or two influenza B strains that circulate in the human population, respectively. In this review we briefly compare trivalent and quadrivalent inactivated influenza vaccines (TIV and QIV) with live attenuated influenza vaccines (LAIV). The use of the latter vaccine type in children age 2-8 has been disrecommended recently by the American Centers for Disease Control and Prevention due to inferior vaccine effectiveness in this age group in recent seasons. This recommendation will favor the use of TIV and QIV over LAIV in the near future. However, there is much evidence from studies in humans that illustrate the benefit of LAIV and we discuss some of the mechanisms that contribute to broader protection against influenza viruses of different subtypes induced by natural infection and LAIV. The future challenge will be to apply these insights to allow induction of broader and long-lasting protection provided by TIV and QIV vaccines, for example, by the use of adjuvants or combining LAIV with TIV and QIV. Other immune factors than serum hemagglutination inhibiting antibodies have shown to correlate with protection provided by TIV and QIV, which illustrates the need for other correlates of protection than hemagglutination inhibition by serum antibodies and justifies more focus on influenza antigens in the TIV and QIV other than hemagglutinin.