Abstract
The efficacy of the intranasally (i.n.) delivered live attenuated influenza vaccine (LAIV) is variable and, in some seasons, suboptimal. In this study, we report that LAIV exhibits cross-protective efficacy in mice, potentially associated with cellular immunity as opposed to antigen-specific antibody responses. However, pre-exposure to the intramuscularly (i.m.) delivered inactivated influenza vaccine (IIV) severely impaired LAIV-induced cross-protection against heterologous challenge, potentially by inhibiting replication of LAIV. Our findings suggest that pre-existing immunity afforded by IIV suppresses cross-protective T cell immunogenicity of LAIV.
Highlights
The current quadrivalent influenza vaccines contain antigens derived from four influenza viruses of subtypes A and B
To investigate the impact of pre-existing immunity on live attenuated influenza vaccine (LAIV) efficacy, mice were first i.m. vaccinated with inactivated influenza vaccine (IIV) or PBS and i.n. immunized with LAIV or PBS (Figure 1a)
459 IIV or PBS and i.n. immunized with LAIV or PBS (Figure 1a)
Summary
The current quadrivalent influenza vaccines contain antigens derived from four influenza viruses of subtypes A and B. These vaccines are mainly either inactivated influenza vaccines (IIVs) (including subunit or split-virion), live attenuated influenza vaccines (LAIVs) or recombinant hemagglutinin (HA) vaccines. In experimental animal challenge models of influenza, LAIV consistently elicited superior protective immune responses compared to IIV [1,2], including cross-protective immunity [3]. The clinical report on inferior efficacy of LAIV compared to IIV was in striking contrast to those findings made in animal models across several studies where LAIV was shown to be superior [1,2,3,5]. The discrepancies in LAIV efficacy between animal models and humans raise a question about the predictive value of animal models used for influenza vaccine research, especially if the vaccination context between animal studies and the clinic vary significantly
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