{"doi":"10.1101/2022.09.12.507712","title":"The Respiratory Syncytial Virus G Protein Enhances the Immune Responses to the RSV F Protein in an Enveloped Virus-like Particle Vaccine Candidate","abstract":"Abstract Respiratory syncytial virus (RSV) is a serious human respiratory pathogen, but no RSV vaccine has been licensed. Many of the vaccine candidates are focused on the viral F protein. However, it is the G protein that binds the likely receptor, CX3CR1, in human alveolar lung cells raising the question of the importance of the G protein in vaccine candidates. Using virus-like particle (VLP) vaccine candidates, we have directly compared VLPs containing only the pre-fusion F protein, only the G protein, or both glycoproteins. We report that VLPs containing both glycoproteins bind to anti-F protein specific monoclonal antibodies differently than VLPs containing only the pre-fusion F protein. Using RSV naïve cotton rats as an animal model, we have found that VLPs assembled only with the pre-F protein stimulated extremely weak neutralizing antibody (NAb) titers as did VLPs assembled with G protein. However, VLPs assembled with both glycoproteins stimulated quite robust neutralizing antibody titers, titers that were significantly higher than the combined titers induced by pre-F only or G only VLPs. VLPs assembled with both glycoproteins induced improved protection of the animals from RSV challenge compared to pre-F VLPs and induced significantly higher levels of antibodies specific for F protein antigenic sites 0, site III, and AM14 binding site compared with VLPs containing only the pre-F protein. These combined results indicate that assembly of pre-F protein with G protein in VLPs further stabilized the pre-fusion conformation or otherwise altered the conformation of the F protein increasing the induction of protective antibodies. Importance RSV causes significant disease in infants, young children, and the elderly. Thus, development of an effective vaccine for these populations is a priority. Most ongoing efforts in RSV vaccine development have focused on the viral fusion (F) protein, however, the importance of inclusion of G in vaccine candidates is unclear. Here, using VLPs assembled with only the F protein or only the G protein or both glycoproteins, we show that VLPs assembled with both glycoproteins are a far superior vaccine, in a cotton rat model, than VLPs containing only F protein or only G protein. The results show that the presence of G protein in the VLPs influences the conformation of the F protein and the immune responses to F protein resulting in significantly higher neutralizing antibody titers and better protection from RSV challenge. These results suggest that inclusion of G protein in a vaccine candidate may improve its effectiveness.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":301868,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9582,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":993340,"name":"Bin Luo","orcid":"0000-0003-1061-1019","position":1,"is_corresponding":false},{"id":993869,"name":"Zhiyun Wen","orcid":null,"position":2,"is_corresponding":false},{"id":993341,"name":"Lan Zang","orcid":"0000-0001-7602-631X","position":3,"is_corresponding":false},{"id":993342,"name":"Eberhard Dürr","orcid":"0000-0003-0601-1117","position":4,"is_corresponding":false},{"id":993343,"name":"Trudy G. Morrison","orcid":"0000-0003-2800-7717","position":5,"is_corresponding":false},{"id":993868,"name":"Lori M. Cullen","orcid":null,"position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T00:32:06.309890Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}