Immune Responses Elicited by Live Attenuated Influenza Vaccines as Correlates of Universal Protection against Influenza Viruses

Abstract

Influenza virus infection remains a major public health challenge, causing significant morbidity and mortality by annual epidemics and intermittent pandemics. Although current seasonal influenza vaccines provide efficient protection, antigenic changes of the viruses often significantly compromise the protection efficacy of vaccines, rendering most populations vulnerable to the viral infection. Considerable efforts have been made to develop a universal influenza vaccine (UIV) able to confer long-lasting and broad protection. Recent studies have characterized multiple immune correlates required for providing broad protection against influenza viruses, including neutralizing antibodies, non-neutralizing antibodies, antibody effector functions, T cell responses, and mucosal immunity. To induce broadly protective immune responses by vaccination, various strategies using live attenuated influenza vaccines (LAIVs) and novel vaccine platforms are under investigation. Despite superior cross-protection ability, very little attention has been paid to LAIVs for the development of UIV. This review focuses on immune responses induced by LAIVs, with special emphasis placed on the breadth and the potency of individual immune correlates. The promising prospect of LAIVs to serve as an attractive and reliable vaccine platforms for a UIV is also discussed. Several important issues that should be addressed with respect to the use of LAIVs as UIV are also reviewed.

Universal Live-Attenuated Influenza Vaccine Candidates Expressing Multiple M2e Epitopes Protect Ferrets against a High-Dose Heterologous Virus Challenge

“…Importantly, there was no reduction in homologous HAI or serum IgG titers in ferrets immunized with recombinant LAIV+4M2e candidates, relative to the traditional LAIV virus, suggesting that none of the genetic modifications had an impact of influenza virus-specific humoral immunity. In line with previously published data, immunization with unmodified influenza virus (i.e., H3N2 LAIV) did not elicit notable levels of M2e-binding antibodies in ferrets [ 33 ]. However, the insertion of the 4M2e cassette into LAIV genome significantly increased the M2e-specific antibody levels, with the LAIV/HA+4M2e variant being remarkably more immunogenic than the LAIV/NS+4M2e counterpart.…”

Live attenuated virus vaccine protects against SARS-CoV-2 variants of concern B.1.1.7 (Alpha) and B.1.351 (Beta)

“…Excellent clinical protection, consistent with the absence of replication-competent virus in the lungs of challenged animals, and robust antibody responses shortly after challenge do, however, demonstrate the strong protective potential of this vaccine against different SARS-CoV-2 variants. In addition, vaccination with a live attenuated virus may offer better protection from (re)infection than vaccines that carry only a single antigen, because all SARS-CoV-2 proteins may trigger stronger cytotoxic T cell responses ( 38 ).…”

Universally Immune: How Infection Permissive Next Generation Influenza Vaccines May Affect Population Immunity and Viral Spread

“…It has been previously theorised that sub-neutralising antibody levels and activation of FcγRI and FcγRIIA could promote viral cell entry, replication, and subsequent antigen presentation and immunogenicity of live attenuated viral vaccines [ 127 ]. However, a recent review has noted that in the context of influenza, LAIVs have been repeatedly shown to be safe and effective in animal models with no indications of VAERD or ADE [ 128 ]. A study by Winarski et al sought to evaluate the effect of monoclonal antibodies (mAbs) on influenza disease in a mouse model [ 129 ].…”