Research Article: The effect of respiratory viruses on immunogenicity and protection induced by a candidate universal influenza vaccine in mice

Date Published: April 15, 2019

Publisher: Public Library of Science

Author(s): Janelle Rowell, Chia-Yun Lo, Graeme E. Price, Julia A. Misplon, Roberta L. Crim, Priyanka Jayanti, Judy Beeler, Suzanne L. Epstein, Steven M. Varga.


Current approaches to influenza control rely on vaccines matched to viruses in circulation. Universal influenza vaccines would offer the advantage of providing broad protection against diverse strains of influenza virus. Candidate universal vaccines are developed using model systems, often testing in naïve animals. Yet the human population is not naïve, having varied immune histories that include exposure to viruses. We studied a candidate universal influenza vaccine (replication deficient adenoviruses expressing the conserved influenza A antigens NP and M2 [A/NP+M2-rAd]) given intranasally, the route previously shown to be most effective. To model recipients exposed to viruses, we used mice given rhinovirus (RV1B), respiratory syncytial virus (RSV-A2), influenza B virus, or influenza A virus before or after universal influenza vaccine. Vaccine performance was assessed by measuring immune responses to NP and M2, and monitoring weight loss and survival following influenza A challenge. Prior influenza A virus infection enhanced the response to the vaccine by priming to conserved influenza A antigens. RSV-A2 or RV1B had no effect on antibody responses to NP and M2 in serum. None of the viruses inhibited the ability of the vaccine to protect against influenza A virus challenge. The study demonstrates that the usefulness of this universal vaccine is not confined to the immunologically naïve and supports possible use in a human population with a varied history of respiratory infections.

Partial Text

Universal influenza vaccines have the potential to reduce the disease burden of seasonal and pandemic influenza. We have developed a candidate universal vaccine based on conserved influenza A virus (IAV) antigens nucleoprotein (A/NP) and matrix 2 (M2). Our previous studies demonstrated that DNA priming followed by boosting with a mixture of recombinant adenoviruses expressing A/NP and M2 (A/NP+M2-rAd) [1, 2] or a single intranasal dose of A/NP+M2-rAd [3, 4] protect naïve animals against subsequent IAV challenge of diverse strains and subtypes, preventing death and severe weight loss.

Immune history may have an impact on responses to a subsequent infection or immunization. Prior research has extensively described the phenomenon of immune responses to prior infections altering the responses to subsequent infection with a different pathogen [13]. Thus, testing candidate vaccines in animals with previous exposures can provide additional information relevant to human vaccination.