A mucosal adjuvant for the inactivated poliovirus vaccine

Abstract

The eradication of poliovirus from the majority of the world has been achieved through the use of two vaccines: the inactivated poliovirus vaccine (IPV) and the live-attenuated oral poliovirus vaccine (OPV). Both vaccines are effective at preventing paralytic poliomyelitis, however, they also have significant differences. Most importantly for this work is the risk of revertant virus from OPV, the greater cost of IPV, and the low mucosal immunity induced by IPV. We and others have previously described the use of an alphavirus-based adjuvant that can induce a mucosal immune response to a co-administered antigen even when delivered at a non-mucosal site. In this report, we describe the use of an alphavirus-based adjuvant (GVI3000) with IPV. The IPV-GVI3000 vaccine significantly increased systemic IgG, mucosal IgG and mucosal IgA antibody responses to all three poliovirus serotypes in mice even when administered intramuscularly. Furthermore, GVI3000 significantly increased the potency of IPV in rat potency tests as measured by poliovirus neutralizing antibodies in serum. Thus, an IPV-GVI3000 vaccine would reduce the dose of IPV needed and provide significantly improved mucosal immunity. This vaccine could be an effective tool to use in the poliovirus eradication campaign without risking the re-introduction of revertant poliovirus derived from OPV.

Keywords: Adjuvant; Alphavirus; Inactivated poliovirus vaccine; Mucosal immunity.

Figure 1. Humoral immune response to IPV and GVI3000 in mice

BALB/c mice (6 per group) were primed and boosted i.m. with IPV alone or co-administered with GVI3000. The levels of (A) IgG, (B) IgG2a and (C) IgG1 serotype-specific antibodies to PV in the serum were determined at 3 weeks post-boost by ELISA. Values represent the reciprocal of the mean endpoint dilution ± SEM. A ratio between the endpoint dilutions of IgG2a and IgG1 is shown in (D) and the dashed line represents a ratio of 1. Statistical significance, ns= not significant, *=p<0.05, **=p<0.01. Similar significant differences in serum IgG titers with and without adjuvant were achieved in two separate experiments using BALB/c mice.

Figure 2. Mucosal immune response to IPV and GVI3000 in mice

BALB/c mice (6 per group) were primed and boosted i.m. with IPV alone or co-administered with GVI3000. The levels of serotype-specific IgA in fecal extracts at 10 days post-boost were determined by ELISA. Values represent the mean endpoint dilution ± SEM. Statistical significance, ***=p<0.001. Similar significant differences in mucosal IgA titers with and without adjuvant were achieved in two separate experiments using BALB/c mice.

Figure 3. Antibody response to IPV and GVI3000 in different lymphoid organs

BALB/c mice (10 per group) were primed and boosted i.m. with IPV alone or co-administered with GVI3000. 14 days post-boost, the spleen, popliteal lymph nodes (PLN), and intestine were harvested and cultured. On day 7 the levels of serotype-specific IgG (A) and IgA (B) in culture supernatants were determined. Values represent the mean endpoint dilution ± SEM. Statistical significance, *=p<0.05, **=p<0.01, ***=p<0.001.

Figure 4. IPV and GVI3000 in a rat IPV potency model

Outbred rats (n=15/group) were primed and boosted i.m. with IPV alone or with GVI3000. Neutralizing antibody titers against PV types 1, 2 and 3 were determined at 21 days post-prime (A) and 21 days post-boost (B). Each symbol represents an individual titer and the line indicates the group mean. The dashed line is the last dilution tested for neutralizing antibody and represents the upper limit of detection. Statistical significance, *=p<0.05, **=p<0.01, ***=p<0.001.