In the present study, we constructed and prepared a dual subunit vaccine candidate, Gcf-HA1, containing RSV G protein fragment and HA1 domain of influenza PR8 virus and investigated the immunogenicity and protective immunity generated by mucosal vaccination of CT-adjuvanted Gcf-HA1.
So far, myriad of RSV vaccine candidates have targeted the two viral surface envelope proteins, G and F, due to their ability to induced neutralizing antibody responses, the presence of which correlates with protection against RSV infection. In our study, RSV G fragment containing the central conserved region was used as the vaccine candidate against RSV infection. The RSV G fragment used in our study corresponds to the amino acid residues 131 to 230 in RSV A2 G protein, which includes the 13 residue-long amino acid sequence that are fully conserved between the two known RSV strains A and B as well as cysteine-noose region containing the CX3C chemokine motif (14
). Moreover, multiple protective B cell epitopes were identified within this fragment (15
) corroborating our approach of using RSV G fragment as vaccine candidate an appropriate strategy in eliciting antibody-mediated protection against RSV infection.
The hemagglutinin is the major glycoprotein and critical viral target structure for the immune defense mechanisms. Also, the influenza virus can escape the anti-viral immunity of the host population through either antigenic drift or antigenic shift. HA is split into the glycoprotein subunits HA1 and HA2. We targeted HA1 containing most of the antigenic epitopes of the HA glycoprotein. HA1 region could be structurally defined by a disulfide bond between two conserved cysteines, and strongly induces specific neutralizing antibody (16
). In a previous study, it has been shown that HA1 is highly immunogenic and provides a specific neutralizing antibody, resulting in effective protection against a lethal challenge of influenza virus in the mouse model (17
There are several advantages of developing recombinant multiplex vaccines that target multiple pathogens. First, administration composite vaccines can potentially offer protection against multiple pathogens as our results indicate that mice vaccinated with Gcf-HA1 fusion protein were protected against both RSV and influenza virus infections. Moreover, use of multiplex vaccines can practically reduce the number of inoculations and potentially minimize the inconvenience that may otherwise arise from multiple visits to hospitals for the reception of single-pathogen-specific vaccines. Further, mucosal vaccination is a non-invasive and convenient administration method and targets specific mucosal area, which are optimal properties of vaccines against respiratory pathogens such as RSV and influenza virus. Also, the production of recombinant composite vaccines via bacterial expression system may be more cost-effective than the current methods of producing licensed-vaccines for various pathogens. Thus, our study provides strong evidence that Gcf-HA1 could be further developed as a dual vaccine against two important respiratory pathogens.