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.
Highlights
Respiratory syncytial virus (RSV) is a negative sense, single-stranded RNA virus belonging to the paramyxoviridae family
It was previously shown that a.a. residues 183–195 of G core fragment of RSV A2 (GcfA) functions as a CD4 T-cell epitope that is necessary for induction of a strong antibody response, while the same region of G core fragment of RSV B1 subtype (GcfB) lacks T-cell epitope functionality and induces a relatively weak antibody response [29]
In order to investigate whether mucosal GcfAB immunization can elicit an antibody responses against both RSV A and B subtypes, BALB/c mice were immunized twice via intranasal (IN) or sublingual (SL) routes with 20 μg of GcfAB plus 2 μg of cholera toxin (CT) as a mucosal adjuvant (Fig 2A)
Summary
Respiratory syncytial virus (RSV) is a negative sense, single-stranded RNA virus belonging to the paramyxoviridae family. RSV is divided into two major subtypes, RSV A and B, depending on the sequence of attachment of the (G) glycoprotein [2, 3]. According to reports, both RSV subtypes co-circulate alternately at 1-2-year intervals during each RSV epidemic [4], and > 60% of infants are infected during their first RSV season, and most children who are exposed to RSV in their early life experience secondary RSV infection [5]. Repeated natural RSV infections occur throughout life owing to an absence of long-term immunity against RSV subtypes [6].
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