Conventional influenza vaccines influence the efficacy of a candidate universal influenza vaccine in mice

Universal influenza vaccines are designed to protect against diverse strains of influenza virus. In a pandemic, universal vaccines could be life-saving. Candidate vaccines are usually tested in naive animals, despite intended use in the human population that has a varied immune history, including responses to vaccination. To be more relevant to humans, we tested a candidate universal influenza vaccine in mice with a history of conventional vaccination. Female BALB/c mice were given two intramuscular doses of inactivated influenza vaccine (IIV) or diphtheria and tetanus toxoids vaccine (DT), one month apart. Another group had two intranasal (i.n.) doses of live attenuated influenza virus (LAIV). One month after the second dose, mice were given the universal vaccine, recombinant adenoviruses expressing influenza A NP and M2 (rAd-NP+M2, i.n.). Antibody responses to universal vaccine antigens NP and M2 were assessed by ELISA. T-cell responses to antigens were determined by IFN-γ ELISPOT. Mice were challenged with mouse-adapted A/FM/1/47 (H1N1) and subsequent weight loss determined rAd-NP+M2 efficacy. Efficacy was enhanced, inhibited or unaffected by prior history. Mice given Afluria IIV and LAIV lost less weight and had a greater antibody and T-cell response to NP than mice without prior vaccination, which are examples of enhanced rAd-NP+M2 efficacy. Inhibited vaccine efficacy was observed in mice that received Fluvirin IIV and mice had low IgG2a antibodies to NP and M2. Fluzone IIV and DT had no effect on rAd-NP+M2 efficacy. This study demonstrates that the protection by the universal influenza vaccine may be affected by a history of conventional vaccination, and suggests that performance in humans would be influenced by immune history.