Abstract
Influenza viruses continuously circulate in the human population and escape recognition by virus neutralizing antibodies induced by prior infection or vaccination through accumulation of mutations in the surface proteins hemagglutinin (HA) and neuraminidase (NA). Various strategies to develop a vaccine that provides broad protection against different influenza A viruses are under investigation, including use of recombinant (r) viral vectors and adjuvants. The replication-deficient modified vaccinia virus Ankara (MVA) is a promising vaccine vector that efficiently induces B and T cell responses specific for the antigen of interest. It is assumed that live vaccine vectors do not require an adjuvant to be immunogenic as the vector already mediates recruitment and activation of immune cells. To address this topic, BALB/c mice were vaccinated with either protein- or rMVA-based HA influenza vaccines, formulated with or without the saponin-based Matrix-M™ adjuvant. Co-formulation with Matrix-M significantly increased HA vaccine immunogenicity, resulting in antigen-specific humoral and cellular immune responses comparable to those induced by unadjuvanted rMVA-HA. Of special interest, rMVA-HA immunogenicity was also enhanced by addition of Matrix-M, demonstrated by enhanced HA inhibition antibody titres and cellular immune responses. Matrix-M added to either protein- or rMVA-based HA vaccines mediated recruitment and activation of antigen-presenting cells and lymphocytes to the draining lymph node 24 and 48 h post-vaccination. Taken together, these results suggest that adjuvants can be used not only with protein-based vaccines but also in combination with rMVA to increase vaccine immunogenicity, which may be a step forward to generate new and more effective influenza vaccines.
Highlights
IntroductionInfluenza A (H1N1 and H3N2) and B viruses cause respiratory tract infections and are responsible for substantial morbidity and mortality during seasonal epidemics, in patients at high risk, such as the elderly
We show that the immunogenicity of both HA protein- and modified vaccinia virus Ankara (MVA)-based influenza vaccines was enhanced by Matrix-M adjuvant
The IgG2a responses after the second vaccination were comparable between adjuvanted HA groups and both rMVA-HA vaccine groups and were elevated compared to the unadjuvanted HA group (Fig. 1d)
Summary
Influenza A (H1N1 and H3N2) and B viruses cause respiratory tract infections and are responsible for substantial morbidity and mortality during seasonal epidemics, in patients at high risk, such as the elderly. Due to accumulation of mutations in the surface proteins hemagglutinin (HA) and neuraminidase (NA), the antigenic properties of the virus change continuously, resulting in escape from recognition by neutralizing antibodies induced by prior infection or vaccination [1,2,3]. Avian influenza viruses of various subtypes have been shown to infect humans sporadically [4,5,6]. Since virus neutralizing antibodies to these viruses are virtually absent in the human population, they are considered to have pandemic potential
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