{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:12:24Z","timestamp":1774933944473,"version":"3.50.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T00:00:00Z","timestamp":1702944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Respiratory syncytial virus (RSV) vaccines targeting the fusion glycoprotein (F protein) are highly effective clinically in preventing RSV challenges. The attachment glycoprotein (G protein) is a potentially effective vaccine antigen candidate, as it is important for cell adhesion during infection. However, vaccine-associated enhanced diseases in mice, such as eosinophilic lung inflammation following RSV challenge, are a concern with G protein vaccines. This study aimed to design an effective G protein vaccine with enhanced safety and efficacy by evaluating the efficacy and adverse reactions of vaccines composed of different recombinant G proteins and adjuvants in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice were subcutaneously immunized with glycosylated G protein expressed in mammalian cells (mG), non-glycosylated G protein expressed in <jats:italic>Escherichia coli<\/jats:italic> (eG), or F protein with or without aluminum salts (alum), CpG oligodeoxynucleotide (CpG ODN), or AddaVax. After vaccination, the levels of G-specific antibody and T-cell responses were measured. The immunized mice were challenged with RSV and examined for the viral load in the lungs and nasal turbinates, lung-infiltrating cells, and lung pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>mG with any adjuvant was ineffective at inducing G-specific antibodies and had difficulty achieving both protection against RSV challenge and eosinophilia suppression. In particular, mG+CpG ODN induced G-specific T helper 1 (Th1) cells but only a few G-specific antibodies and did not protect against RSV challenge. However, eG+CpG ODN induced high levels of G-specific antibodies and Th1 cells and protected against RSV challenge without inducing pulmonary inflammation. Moreover, the combination vaccine of eG+F+CpG ODN showed greater protection against upper respiratory tract RSV challenge than using each single antigen vaccine alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These results indicate that the efficacy of recombinant G protein vaccines can be enhanced without inducing adverse reactions by using appropriate antigens and adjuvants, and their efficacy is further enhanced in the combination vaccine with F protein. These data provide valuable information for the clinical application of G protein vaccines.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1282016","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T10:32:51Z","timestamp":1702981971000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Non-glycosylated G protein with CpG ODN provides robust protection against respiratory syncytial virus without inducing 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