Advax®-adjuvanted inactivated influenza vaccine provides accelerated protection of mice via early induction of an influenza-specific IgM response

It would be advantageous if a strategy could be found to accelerate vaccine induction of anti-influenza adaptive immunity to more rapidly protect frontline workers and other vulnerable individuals during virus outbreaks. This study asked whether Advax® delta inulin adjuvant could accelerate the kinetics of protection afforded by a single dose of inactivated influenza vaccine (IIV) in two different strains of mice. A single dose of Advax®-adjuvanted IIV, but not IIV alone, gave complete protection if given 7 or 3 days before, and even when given at the same time as virus challenge (same day protection). Co-administration of both IIV and Advax® were critical to obtaining robust same day protection which was not seen with the individual vaccine components. Same day protection was lost in B-cell deficient μMT mice but was still evident in T cell-depleted mice, confirming its dependence on humoral but not T cell immunity. Day 6 post-challenge serum from protected mice demonstrated elevated influenza-binding IgM which had hemagglutination inhibition activity not seen in mice that received IIV alone. This confirmed that Advax® accelerated the kinetics of anti-influenza IgM production in response to IIV. Influenza protection could be transferred to naïve mice using day 6 sera or purified IgM from Advax®-adjuvanted IIV-immunised mice. Draining lymph nodes from protected mice showed increased CD138⁺ B220⁺ migratory and IgM⁺ extrafollicular, antibody secreting cells. These results show Advax® adjuvant accelerates the kinetics of anti-influenza IgM production in response to IIV thereby enabling the vaccine to protect against an infection acquired at the same time as the immunisation. While further studies are required to confirm that this ability to accelerate humoral immune kinetics extends to other species, including non-human primates, the phenomenon of adjuvant-accelerated IIV protection offers promise as a strategy for development of faster-acting vaccines.