Abstract
Nucleoprotein (NP) and matrix protein 1 (M1) are highly conserved among influenza A viruses and have been attractive targets to develop vaccines to elicit cross-reactive cytotoxic T lymphocytes (CTLs). Yet, external antigens are often presented on major histocompatibility complex class II molecules and elicit humoral immune responses. In this study, we present a physical radiofrequency adjuvant (RFA) to assist recombinant NP and M1 to elicit potent CTL responses. We found recombinant NP/M1 immunization in the presence of RFA could elicit potent anti-NP CTLs and confer significant protection against homologous viral challenges, while NP/M1 immunization alone failed to elicit significant CTL responses or confer significant protection. Interestingly, RFA failed to elicit potent anti-M1 CTL responses or anti-NP or anti-M1 antibody responses. Different from RFA, AddaVax adjuvant was found to significantly increase NP-specific antibody responses but not CTLs. NP/M1 immunization in the presence of RFA or AddaVax similarly reduced body weight loss, while only the former significantly increased the survival. We further found NP/M1 immunization in the presence of RFA did not significantly increase serum IL-6 release (a systemic inflammatory mediator) and rather reduced serum IL-6 release after boost immunization. NP/M1 immunization in the presence of RFA did not induce significant local reactions or increase body temperature of mice. The high potency and safety strongly support further development of RFA-based recombinant NP/M1 vaccine to elicit cross-protective immunity.
Highlights
Vaccine remains the most effective and cost-effective means to control influenza [1].Currently approved influenza vaccines mainly stimulate strain-specific humoral immune responses against surface antigen hemagglutinin (HA) and are ineffective to protect against strains that have undergone antigenic drifts or shifts [1,2]
We further found NP/matrix protein 1 (M1) immunization in the presence of radiofrequency adjuvant (RFA) did not significantly increase serum IL-6 release and rather reduced serum IL-6 release after boost immunization
This study explores whether RFA could elicit potent cytotoxic T lymphocytes (CTLs) responses against recombinant NP and M1 protein vaccines and confer protection against influenza viral challenges in murine models
Summary
Approved influenza vaccines mainly stimulate strain-specific humoral immune responses against surface antigen hemagglutinin (HA) and are ineffective to protect against strains that have undergone antigenic drifts or shifts [1,2]. Current influenza vaccines need to be manufactured and immunized annually to provide updated protection against potentially different circulating strains [1,2]. Universal influenza vaccines targeting conserved influenza internal antigens attracted significant attention and a number of universal influenza vaccine candidates based on internal antigens are under active development [3]. These types of vaccines mainly induce cytotoxic T lymphocytes (CTLs) to confer cross-protection [4]
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