Melanie Carroll , Heather B. Fox , Anh Tran , Gowri Chellappan , Leonardo V. Rojas , Geetha Karengil , Fataneh Karandish , John W. Langston , Brent M. Fall , Mary M. Whalen , Michael J. McCluskie , Yves Durocher , Anup Datta , Subhash V. Kapre , Ivan A. Olave
{"title":"SARS-CoV-2 conjugate vaccine elicits robust immune responses that can protect against evolving variants.","authors":"Melanie Carroll , Heather B. Fox , Anh Tran , Gowri Chellappan , Leonardo V. Rojas , Geetha Karengil , Fataneh Karandish , John W. Langston , Brent M. Fall , Mary M. Whalen , Michael J. McCluskie , Yves Durocher , Anup Datta , Subhash V. Kapre , Ivan A. Olave","doi":"10.1016/j.vaccine.2025.126988","DOIUrl":null,"url":null,"abstract":"<div><div>The SARS-CoV-2 pandemic necessitated effective vaccines that can endure antigenic mutations. Here we demonstrate highly immunogenic conjugate vaccines that elicit broad cross-neutralization to variants of concern (VOC) in animal studies. By utilizing protein-protein conjugation and Toll-Like Receptor (TLR) agonist adjuvants we achieve enhanced immunogenicity compared to unconjugated equivalents. These vaccine candidates induced broad cross-protection against several VOC, a characteristic lacking in early COVID-19 vaccines. Murine neutralizing antibody (nAb) titers from animals vaccinated with Beta-only conjugates were equivalent between Beta, Delta, Omicron BA.1, BA.2, and BA.4/BA.5 variants, which were circulating up to three years after the antigenic Beta strain. Additionally, Beta-Delta bivalent conjugate vaccines readily prevented disease in hamster challenge. Together this demonstrates a vaccine with remarkably broad cross-protection and potential to protect for extended periods despite mutations, without requiring modified boosters or antigen adaption. These techniques can be applied to more recent SARS-CoV-2 strains, and other viruses, highlighting the benefits of protein-protein conjugation coupled with TLR agonist secondary adjuvants.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"54 ","pages":"Article 126988"},"PeriodicalIF":4.5000,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Vaccine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0264410X25002853","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The SARS-CoV-2 pandemic necessitated effective vaccines that can endure antigenic mutations. Here we demonstrate highly immunogenic conjugate vaccines that elicit broad cross-neutralization to variants of concern (VOC) in animal studies. By utilizing protein-protein conjugation and Toll-Like Receptor (TLR) agonist adjuvants we achieve enhanced immunogenicity compared to unconjugated equivalents. These vaccine candidates induced broad cross-protection against several VOC, a characteristic lacking in early COVID-19 vaccines. Murine neutralizing antibody (nAb) titers from animals vaccinated with Beta-only conjugates were equivalent between Beta, Delta, Omicron BA.1, BA.2, and BA.4/BA.5 variants, which were circulating up to three years after the antigenic Beta strain. Additionally, Beta-Delta bivalent conjugate vaccines readily prevented disease in hamster challenge. Together this demonstrates a vaccine with remarkably broad cross-protection and potential to protect for extended periods despite mutations, without requiring modified boosters or antigen adaption. These techniques can be applied to more recent SARS-CoV-2 strains, and other viruses, highlighting the benefits of protein-protein conjugation coupled with TLR agonist secondary adjuvants.
期刊介绍:
Vaccine is unique in publishing the highest quality science across all disciplines relevant to the field of vaccinology - all original article submissions across basic and clinical research, vaccine manufacturing, history, public policy, behavioral science and ethics, social sciences, safety, and many other related areas are welcomed. The submission categories as given in the Guide for Authors indicate where we receive the most papers. Papers outside these major areas are also welcome and authors are encouraged to contact us with specific questions.