Inactivated influenza virus vaccines: the future of TIV and QIV

Abstract

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 tri- 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 to 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, e.g. 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.

Influenza Virus Hemagglutinin Stalk-Specific Antibodies in Human Serum are a Surrogate Marker for In Vivo Protection in a Serum Transfer Mouse Challenge Model

“…In the absence of preexisting memory cells against H5 head epitopes, these cells overcome the often-observed dominance of HA head-specific B cells ( 21 , 22 ). The increase of H1 stalk-reactive antibodies in the TIV vaccination group was low (1.3-fold GMI; 95% CI, 1.1 to 1.5), which is consistent with an antibody response that preferentially targets the HA head domain ( 23 ).…”

Polyanhydride Nanovaccine Induces Robust Pulmonary B and T Cell Immunity and Confers Protection Against Homologous and Heterologous Influenza A Virus Infections

“…Traditionally, the spread of IAV has been prevented by two vaccination strategies: inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV). Both IIV and LAIV primarily provide systemic immunity by inducing IAV-specific antibody responses (3,4). However, it is less clear if these vaccination strategies generate robust de novo IAV-specific CD4 or CD8 T cell responses within the lower lung mucosa (4)(5)(6)(7).…”

Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans

“…Seasonal influenza infections are prevented and controlled through annual vaccination campaigns to decrease IAV infections and viral transmission as well as to reduce their negative impact in the global economy. However, although vaccination remains the most effective approach to protect the population from seasonal infections, the effectiveness of current vaccination approaches is suboptimal [16,[31][32][33][39][40][41][42][43][44]. Thus, the production of improved prophylactic approaches, including universal vaccines, are highly desired.…”

“…Notably, the efficacy of vaccines against IAV infections can fluctuate and there is a significant immune response variability across the population. Factors such as previous exposure to IAV infections or vaccines, age, and the closeness of the match between the vaccine and circulating strains are important to explain differences in vaccine effectiveness between seasons and group populations [44,46,[150][151][152]. However, multiple reports have demonstrated that the host genetic background and polymorphisms on key immune response genes modulate the immune response to infection or vaccination [153][154][155][156][157][158][159][160].…”