{"doi":"10.1093/infdis/jiad519","title":"The Novavax Heterologous Coronavirus Disease 2019 Booster Demonstrates Lower Reactogenicity Than Messenger RNA: A Targeted Review","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Coronavirus disease 2019 (COVID-19) continues to be a global health concern, and booster doses are necessary for maintaining vaccine-mediated protection, limiting the spread of severe acute respiratory syndrome coronavirus 2. Despite multiple COVID-19 vaccine options, global booster uptake remains low. Reactogenicity, the occurrence of adverse local/systemic side effects, plays a crucial role in vaccine uptake and acceptance, particularly for booster doses. We conducted a targeted review of the reactogenicity of authorized/approved messenger RNA (mRNA) and protein-based vaccines demonstrated by clinical trials and real-world evidence. It was found that mRNA-based boosters show a higher incidence and an increased severity of reactogenicity compared with the Novavax protein-based COVID-19 vaccine (NVX-CoV2373). In a recent study from the National Institute of Allergy and Infectious Diseases, the incidence of pain/tenderness, swelling, erythema, fatigue/malaise, headache, muscle pain, or fever was higher in individuals boosted with BNT162b2 (0.4% to 41.6% absolute increase) or mRNA-1273 (5.5% to 55.0% absolute increase) compared with NVX-CoV2373. Evidence suggests that NVX-CoV2373, when utilized as a heterologous booster, demonstrates less reactogenicity compared with mRNA vaccines, which, if communicated to hesitant individuals, may strengthen booster uptake rates worldwide.</jats:p>\n               <jats:p>Clinical Trials Registration NCT04889209.</jats:p>","journal":"The Journal of Infectious Diseases","year":2024,"id":604821,"datarank":0.6450026416493037,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.18134627364555614,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.18134627364555614,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":13,"citers_with_citation_signal":9,"citers_with_endowment":9,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1551915,"name":"Matthew Rousculp","orcid":null,"position":1,"is_corresponding":false},{"id":1551917,"name":"John Macbeth","orcid":null,"position":2,"is_corresponding":false},{"id":720944,"name":"Hadi Beyhaghi","orcid":"0000-0003-2862-9663","position":3,"is_corresponding":false},{"id":1551918,"name":"Bruce T Seet","orcid":null,"position":4,"is_corresponding":false},{"id":720943,"name":"Seth Toback","orcid":"0000-0002-5838-812X","position":5,"is_corresponding":false},{"id":711152,"name":"Anthony M. Marchese","orcid":"0000-0001-8468-9666","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The Novavax Heterologous Coronavirus Disease 2019 Booster Demonstrates Lower Reactogenicity Than Messenger RNA: A Targeted Review","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Coronavirus disease 2019 (COVID-19) continues to be a global health concern, and booster doses are necessary for maintaining vaccine-mediated protection, limiting the spread of severe acute respiratory syndrome coronavirus 2. Despite multiple COVID-19 vaccine options, global booster uptake remains low. Reactogenicity, the occurrence of adverse local/systemic side effects, plays a crucial role in vaccine uptake and acceptance, particularly for booster doses. We conducted a targeted review of the reactogenicity of authorized/approved messenger RNA (mRNA) and protein-based vaccines demonstrated by clinical trials and real-world evidence. It was found that mRNA-based boosters show a higher incidence and an increased severity of reactogenicity compared with the Novavax protein-based COVID-19 vaccine (NVX-CoV2373). In a recent study from the National Institute of Allergy and Infectious Diseases, the incidence of pain/tenderness, swelling, erythema, fatigue/malaise, headache, muscle pain, or fever was higher in individuals boosted with BNT162b2 (0.4% to 41.6% absolute increase) or mRNA-1273 (5.5% to 55.0% absolute increase) compared with NVX-CoV2373. Evidence suggests that NVX-CoV2373, when utilized as a heterologous booster, demonstrates less reactogenicity compared with mRNA vaccines, which, if communicated to hesitant individuals, may strengthen booster uptake rates worldwide.</jats:p>\n               <jats:p>Clinical Trials Registration NCT04889209.</jats:p>","is_dataset_classified":null,"base_score":3.091042453358316,"endowment":3.091042453358316,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37992183","pmcid":"PMC11326839","openalex_id":"https://openalex.org/W4388892550","authors":[],"funders":[{"funder_name":"Ashfield MedComms","grant_id":"","title":null},{"funder_name":"Inizio company","grant_id":"","title":null},{"funder_name":"Novavax, Inc","grant_id":"","title":null}],"total_grants":3,"fwci":3.5552,"citation_percentile":0.9401618,"influential_citations":0,"citation_trend":[{"year":2024,"count":6},{"year":2025,"count":11},{"year":2026,"count":4}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://academic.oup.com/jid/advance-article-pdf/doi/10.1093/infdis/jiad519/53688747/jiad519.pdf","host_type":"journal"},{"url":"https://academic.oup.com/jid/advance-article-pdf/doi/10.1093/infdis/jiad519/53688747/jiad519.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jid/advance-article-pdf/doi/10.1093/infdis/jiad519/56820166/jiad519.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jid/article-pdf/230/2/e496/58808498/jiad519.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/infdis/jiad519","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37992183","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11326839","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11326839/pdf/jiad519.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11326839","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11326839?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["SARS-CoV-2 and COVID-19 Research","Viral gastroenteritis research and epidemiology","Animal Virus Infections Studies"],"mesh_terms":["COVID-19","SARS-CoV-2","COVID-19 Vaccines","mRNA Vaccines","BNT162 Vaccine","2019-nCoV Vaccine mRNA-1273","Clinical Trials as Topic","Humans","Immunization, Secondary","RNA, Messenger"],"keywords":["Reactogenicity","Heterologous","Booster (rocketry)","Virology","Coronavirus","RNA","Biology","Coronavirus disease 2019 (COVID-19)","Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)","2019-20 coronavirus outbreak","Medicine","Disease","Infectious disease (medical specialty)","Immunology","Genetics","Immunogenicity","Physics","Gene","Immune system","Booster","Mrna Vaccines","Covid-19","Nvx-cov2373"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T00:59:26.390177Z","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":[]}