Intranasal immunization with a single dose of the fusion protein formulated with a combination adjuvant induces long-term protective immunity against respiratory syncytial virus

ABSTRACT

Respiratory syncytial virus (RSV) is the most common cause of respiratory tract infections in both children and elderly people. In this study we evaluated the short- and long-term protective efficacy of a single intranasal (IN) immunization with a RSV vaccine formulation consisting of a codon-optimized fusion (F) protein formulated with poly(I:C), an innate defense regulator peptide and a polyphosphazene (ΔF/TriAdj). This vaccine induced strong systemic and local immune responses, including RSV F-specific IgG1 and IgG2a, SIgA and virus neutralizing antibodies in mice. Furthermore, ΔF/TriAdj promoted production of IFN-γ-secreting T cells and RSV F_85–93-specific CD8⁺ effector T cells. After RSV challenge, no virus was recovered from the lungs of the vaccinated mice. To evaluate the duration of immunity induced by a single IN vaccination, mice were again immunized once with ΔF/TriAdj and challenged with RSV five months later. High levels of IgG1, IgG2a and virus neutralizing antibodies were detected in the ΔF/TriAdj-vaccinated animals. Moreover, this vaccine formulation induced robust local SIgA production and IgA-secreting memory B cell development, and conferred complete protection against subsequent RSV challenge. In conclusion, a single IN vaccination with RSV ΔF protein formulated with TriAdj induced robust, long-term protective immune responses against RSV infection.

KEYWORDS:

• adjuvant
• mucosal immunity
• protection
• RSV
• subunit vaccine

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgements

The authors would like to thank Robert Brownlie, Wayne Connor, Elisa C. Martinez, and Michael Theaker for technical assistance, as well as Sherry Tetland and Jan Erickson for the handling and care of the animals. Published as VIDO manuscript number 799.

Funding

This work was supported by the Krembil Foundation, and grant MOP 119473 from the Canadian Institutes of Health Research (CIHR).