Dual Role of Respiratory Syncytial Virus Glycoprotein Fragment as a Mucosal Immunogen and Chemotactic Adjuvant

Abstract

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease in infancy and early childhood. Despite its importance as a pathogen, there is no licensed vaccine to prevent RSV infection. The G glycoprotein of RSV, a major attachment protein, is a potentially important target for protective antiviral immune responses and has been shown to exhibit chemotactic activity through CX3C mimicry. Here, we show that sublingual or intranasal immunization of a purified G protein fragment of amino acids from 131 to 230, designated Gcf, induces strong serum IgG and mucosal IgA responses. Interestingly, these antibody responses could be elicited by Gcf even in the absence of any adjuvant, indicating a novel self-adjuvanting property of our vaccine candidate. Gcf exhibited potent chemotactic activity in in vitro cell migration assay and cysteine residues are necessary for chemotactic activity and self-adjuvanticity of Gcf in vivo . Mucosal immunization with Gcf also provides protection against RSV challenge without any significant lung eosinophilia or vaccine-induced weight loss. Together, our data demonstrate that mucosal administration of Gcf vaccine elicits beneficial protective immunity and represents a promising vaccine regimen preventing RSV infection.

Baculovirus-expressed virus-like particle vaccine in combination with DNA encoding the fusion protein confers protection against respiratory syncytial virus

“…The FI-RSV immunized group showed an extreme high level of eosinophils with CD45 + CD11c − CD11b + SiglecF + phenotypes (Fig. 8) as previously characterized [30, 31]. This eosinophil phenotypic population was observed at a low level in the BAL fluids from naïve or Fd.VLP immunized mice after RSV challenge infection (Fig.…”

Recombinant influenza virus carrying the conserved domain of respiratory syncytial virus (RSV) G protein confers protection against RSV without inflammatory disease

“…RSV G protein-specific antibodies (IgG, IgG1, and IgG2a) were determined in samples by enzyme-linked immunosorbent assay (ELISA) as previously described (Kim et al, 2012). Briefly, the extracellular domain of RSVG protein with over 95% purity (200 ng/ml, Sino biological, Beijing, China) or inactivated influenza virus (4 μg/ml) was used as a coating antigen.…”

Structure and Function of Respiratory Syncytial Virus Surface Glycoproteins

“…Another group performed vaccination studies in naive mice with a similar peptide (amino acids 131–230) and mucosal immunization, without the addition of an adjuvant. The immunized mice were nearly completely protected from an RSV challenge, without indications of enhanced disease (Kim et al 2012). …”