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Universal vaccine against respiratory syncytial virus A and B subtypes
1Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.
Abstract:
Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in infants, young children, and the elderly. Two subtypes of RSV, A and B, circulate alternately at 1-2-year intervals during epidemics. The attachment glycoprotein (G protein) of RSV is one of the major targets for immune responses. In this study, we generated a recombinant fusion protein, GcfAB, which consists of the central regions (a.a. residues 131-230) of the G proteins of both RSV A (A2 strain) and B (B1 strain) subtypes, and investigated immunogenicity, protective efficacy, and immunopathology. We immunized mice with GcfAB plus cholera toxin as a mucosal adjuvant via intranasal (IN) or sublingual (SL) routes. The IN group showed higher levels of RSV G-specific antibody responses, including serum IgG and mucosal IgA, compared with the SL group. On the contrary, more vigorous RSV G-specific CD4+ T-cell responses were elicited in the SL group than in the IN group after RSV-A but not RSV-B viral challenge. Furthermore, the SL group showed more pulmonary eosinophil recruitment and body weight loss than did the IN group after RSV-A challenge. Both IN and SL immunization with GcfAB provided potential protection against both subtypes of infections. Together, these results suggest that vaccination with GcfAB via an IN route could be a universal vaccine regimen preventing both RSV A and B infections.
Insights
A novel fusion protein, GcfAB, offers potential protection against both Respiratory Syncytial Virus (RSV) A and B subtypes. Intranasal vaccination with GcfAB may be a promising universal RSV vaccine strategy.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Respiratory Syncytial Virus (RSV) causes severe lower respiratory tract infections in vulnerable populations.
- RSV has two main subtypes, A and B, which circulate in alternating epidemics.
- The G protein of RSV is a key target for immune responses and vaccine development.
Purpose of the Study:
- To investigate the immunogenicity, protective efficacy, and immunopathology of a novel recombinant fusion protein (GcfAB) targeting both RSV A and B subtypes.
- To compare the effects of intranasal (IN) versus sublingual (SL) immunization routes using GcfAB with cholera toxin adjuvant.
Main Methods:
- Generation of a fusion protein (GcfAB) comprising central regions of RSV A and B G proteins.
- Immunization of mice with GcfAB and cholera toxin via IN or SL routes.
- Assessment of antibody and T-cell responses, pulmonary eosinophil recruitment, and body weight changes post-RSV challenge.
Main Results:
- Intranasal immunization induced higher RSV G-specific antibody responses (serum IgG, mucosal IgA) than sublingual.
- Sublingual immunization elicited stronger RSV G-specific CD4+ T-cell responses after RSV-A challenge.
- Both IN and SL routes provided protection against RSV A and B infections, with IN showing potentially less immunopathology.
Conclusions:
- GcfAB fusion protein demonstrates immunogenicity and protective potential against both RSV subtypes.
- Intranasal vaccination with GcfAB may represent a universal vaccine strategy for preventing RSV A and B infections.
- The choice of immunization route influences the type and magnitude of immune responses and immunopathology.