Challenge of BALB/c Mice with Respiratory Syncytial Virus Does Not Enhance the Th2 Pathway Induced after Immunization with a Recombinant G Fusion Protein, BBG2NA, in Aluminum Hydroxide

Abstract

The polypeptide of aa 130-230 of the G protein (G2Na) of respiratory syncytial virus (RSV) was fused to BB, the albumin-binding region of streptococcal G protein, producing BBG2Na, which induced protective immune responses in rodent models. Evaluation of the immune response in mice immunized with BBG2Na in the adjuvant alhydrogel revealed high amounts of interleukin (IL)-5 and some IL-4 in splenocytes restimulated in vitro. This is compatible with a Th2 response. The activation of the Th2 pathway in such mice was further supported by the detection of IL-5 and G2Na-specific IgE in vivo. Of interest, in contrast to immunization with formalin-inactivated RSV, immunization of mice with BBG2Na followed by intranasal RSV challenge did not lead to increased production of IL-5- or G2Na-specific IgE. However, IgG1- and IgG2a-specific antibodies were boosted. These results demonstrate that the Th2 pathway is not enhanced by RSV challenge in BBG2Na-immunized mice.

Recurrent Respiratory Syncytial Virus Infections in Allergen-Sensitized Mice Lead to Persistent Airway Inflammation and Hyperresponsiveness

“…This suggests that the enhanced IgE response observed in ASRSV mice is probably due to the increase in IgE Abs specific to RSV. This inference is consistent with previous reports that RSV is capable of inducing an IgE class switch (31,32). The RSV G protein especially mounts an IgE response (33,34).…”

Gamma Interferon-Dependent Protection of the Mouse Upper Respiratory Tract following Parenteral Immunization with a Respiratory Syncytial Virus G Protein Fragment

“…1B). Previous experiments in our laboratories demonstrated that depletion of CD4-positive cells abolished the T-cell proliferation observed after stimulation of immune cells with G2Na (9). Similarly, cell proliferation of G2Na-immunized mice induced by the peptides covering the region from amino acid 182 to 198 was completely eliminated after depletion of CD4-positive cells (data not shown), confirming that it was CD4 mediated.…”

“…Interestingly, previous studies in our laboratories demonstrated that in contrast to the case with formalin-inactivated RSV, although the recombinant G2Na fragment induces a predominant Th2-type T-cell response upon immunization, no production of IL-4, IL-5, or IgE was detected either in sera or in lungs of G2Na-primed mice after live RSV challenge (9,26). These results indicated that the Th2-type memory T cells were not recalled either in lungs or in the periphery in these mice.…”

“…In an earlier study, we found that at least one T-helper-cell epitope was located on G2Na and responsible for the generation of G2Na-specific T-cell proliferation (9). In order to localize the corresponding T-cell determinants on the recombinant G2Na fragment, we used a panel of 12-mer overlapping peptides spanning amino acid residues 130 to 230 of the RSV G protein.…”

“…Interestingly, none of these pathological responses were induced in animal models after immunization with a recombinant, nonglycosylated RSV G protein fragment (called G2Na) produced in Escherichia coli (9,26,28). G2Na comprises residues 130 to 230, including the conserved central domain of RSV G protein (residues 164 to 176) (12).…”