Features of the Human Antibody Response against the Respiratory Syncytial Virus Surface Glycoprotein G

Abstract

Respiratory syncytial virus (RSV) infections are a major cause of serious respiratory disease in infants. RSV occurs as two major subgroups A and B, which mainly differ regarding the surface glycoprotein G. The G protein is important for virus attachment and G-specific antibodies can protect against infection. We expressed the surface-exposed part of A2 strain-derived G (A2-G) in baculovirus-infected insect cells and synthesized overlapping peptides spanning complete A2-G. The investigation of the natural IgG response of adult subjects during a period of one year showed that IgG antibodies (i) recognize G significantly stronger than the fusion protein F0, (ii) target mainly non-conformational, sequential peptide epitopes from the exposed conserved region but also buried peptides, and (iii) exhibit a scattered but constant recognition profile during the observation period. The IgG subclass reactivity profile (IgG1 > IgG2 > IgG4 = IgG3) was indicative of a mixed Th1/Th2 response. Two strongly RSV-neutralizing sera including the 1st WHO standard contained high IgG anti-G levels. G-specific IgG increased strongly in children after wheezing attacks suggesting RSV as trigger factor. Our study shows that RSV G and G-derived peptides are useful for serological diagnosis of RSV-triggered exacerbations of respiratory diseases and underlines the importance of G for development of RSV-neutralizing vaccines.

Neutralization of SARS‐CoV‐2 requires antibodies against conformational receptor‐binding domain epitopes

“…We collected blood samples approximately 8 weeks after acute infection when specific antibodies are in the plateau phase 25,30,31 . The analysis of sera from 253 COVID‐19–convalescent patients showed that the antibody response against the spike protein and RBD is dominated by the IgG isotype, in particular by the IgG 1 subclass which is in agreement with an earlier report 32 and is similar as was found for other respiratory viruses (eg, RV and RSV) which did not induce IgG 3 and IgG 4 responses 20,33 . S‐ and RBD‐specific IgG antibodies indicative of an asymptomatic infection were observed in 2.9% of our control cohort, and their levels were lower than those in the patients with mild or severe symptoms (data not shown).…”

“… 25 , 30 , 31 The analysis of sera from 253 COVID‐19–convalescent patients showed that the antibody response against the spike protein and RBD is dominated by the IgG isotype, in particular by the IgG 1 subclass which is in agreement with an earlier report 32 and is similar as was found for other respiratory viruses (eg, RV and RSV) which did not induce IgG 3 and IgG 4 responses. 20 , 33 S‐ and RBD‐specific IgG antibodies indicative of an asymptomatic infection were observed in 2.9% of our control cohort, and their levels were lower than those in the patients with mild or severe symptoms (data not shown). We did not have access to mucosal secretions but several studies have already investigated the specific immunoglobulin response in nasal secretions, tears, and stool indicating that SARS‐CoV‐2–specific IgA antibodies may occur in such samples in addition to IgG antibodies.…”

“…Immunoglobulin (Ig) response of human or rabbit serum samples of COVID‐19–convalescent patients and healthy control sera to SARS‐CoV‐2–derived proteins was determined by enzyme‐linked immunosorbent assay (ELISA) as previously described. 19 , 20 Details can be found in the articles' Supporting information.…”

Dissociation of the respiratory syncytial virus F protein-specific human IgG, IgA and IgM response

“…In agreement with an earlier study, which reported low RSV-specific IgA responses in individuals which were experimentally infected with RSV we also found a low F-specific IgA response both against the recombinant proteins and peptides 45 . Using serum samples obtained from children who had experienced virus-triggered exacerbations of wheeze and were PCR positive for RSV we found increases of F0 and especially G-specific IgG responses approximately ten weeks after the wheezing exacerbation suggesting infection by RSV as a possible trigger factor 46 .…”

Immune escaping of the novel genotypes of human respiratory syncytial virus based on gene sequence variation

“…Furthermore, Genotypes ON1 and NA1 of RSV-A had similar 3D modeling structures in F and SH proteins but significant differences in G protein among genotypes ON1, NA1, and BA9 (RSV-B) ( Figure 1 ). Accumulating evidence showed that RSV glycoprotein G has important immune modulatory effects during RSV infection, which may induce an exacerbated Th2 type cytokine expression and affect the antiviral response through the modulation of perforin and granzyme B expression ( 21 ). In addition, antibodies induced by the G protein are mainly involved in inhibiting viral replication and in immune modulation by interfering with the antibody-mediated neutralization response.…”