PMID- 37271706 OWN - NLM STAT- MEDLINE DCOM- 20230621 LR - 20230624 IS - 1873-2518 (Electronic) IS - 0264-410X (Print) IS - 0264-410X (Linking) VI - 41 IP - 29 DP - 2023 Jun 29 TI - Immunogenicity and safety of a fourth homologous dose of NVX-CoV2373. PG - 4280-4286 LID - S0264-410X(23)00612-6 [pii] LID - 10.1016/j.vaccine.2023.05.051 [doi] AB - The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has significantly reduced the efficacy of some approved vaccines. A fourth dose of NVX-CoV2373 (5 microg SARS-CoV-2 recombinant spike [rS] protein + 50 microg Matrix-M adjuvant; Novavax, Gaithersburg, MD) was evaluated to determine induction of cross-reactive antibodies to variants of concern. A phase II randomized study (NCT04368988) recruited participants in Australia and the United States to assess a primary series of NVX-CoV2373 followed by two booster doses (third and fourth doses at 6-month intervals) in adults 18-84 years of age. The primary series was administered when the SARS-CoV-2 ancestral strain was prevalent and the third and fourth doses while the Alpha and Delta variants were prevalent in AUS and US. Local/systemic reactogenicity was assessed the day of vaccination and for 6 days thereafter. Unsolicited adverse events (AEs) were reported. Immunogenicity was measured before, and 14 days after, fourth dose administration, using anti-spike serum immunoglobulin G (IgG) and neutralization assays against ancestral SARS-CoV-2 strain and Omicron sublineages. Among 1283 enrolled participants, 258 were randomized to receive the two-dose primary series, of whom 104 received a third dose, and 45 received a fourth dose of NVX-CoV2373. The incidence of local/systemic reactogenicity events increased after the first three doses of NVX-CoV2373 and leveled off after dose 4. Unsolicited AEs were reported in 9 % of participants after dose 4 (none of which were severe or serious). Anti-rS IgG levels and neutralization antibody titers increased following booster doses to a level approximately four-fold higher than that observed after the primary series, with a progressively narrowed gap in response between the ancestral strain and Omicron BA.5. A fourth dose of NVX-CoV2373 enhanced immunogenicity for ancestral and variant SARS-CoV-2 strains without increasing reactogenicity, indicating that updates to the vaccine composition may not be currently warranted. CI - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Alves, Katia AU - Alves K AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. Electronic address: kalves@Novavax.com. FAU - Plested, Joyce S AU - Plested JS AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. Electronic address: jplested@Novavax.com. FAU - Galbiati, Shirley AU - Galbiati S AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. Electronic address: sgalbiati@Novavax.com. FAU - Chau, Gordon AU - Chau G AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. Electronic address: gchau@Novavax.com. FAU - Cloney-Clark, Shane AU - Cloney-Clark S AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. Electronic address: wcloneyclark@Novavax.com. FAU - Zhu, Mingzhu AU - Zhu M AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. Electronic address: mzhu@Novavax.com. FAU - Kalkeri, Raj AU - Kalkeri R AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. Electronic address: rkalkeri@Novavax.com. FAU - Patel, Nita AU - Patel N AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. Electronic address: npatel@Novavax.com. FAU - Smith, Kathy AU - Smith K AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. Electronic address: KaSmith@Novavax.com. FAU - Marcheschi, Alex AU - Marcheschi A AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. Electronic address: amarcheschi@Novavax.com. FAU - Pfeiffer, Susan AU - Pfeiffer S AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. Electronic address: spfeiffer@Novavax.com. FAU - McFall, Heather AU - McFall H AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. Electronic address: mcfall.heather@gmail.com. FAU - Smith, Gale AU - Smith G AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. Electronic address: GSmith@Novavax.com. FAU - Glenn, Gregory M AU - Glenn GM AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. Electronic address: gglenn@Novavax.com. FAU - Dubovsky, Filip AU - Dubovsky F AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. Electronic address: FDubovsky@Novavax.com. FAU - Mallory, Raburn M AU - Mallory RM AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. Electronic address: RMallory@Novavax.com. CN - Novavax 2019nCoV-101 Study Group AD - Novavax, Inc., 21 Firstfield Rd, Gaithersburg, MD 20878, USA. LA - eng SI - ClinicalTrials.gov/NCT04368988 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230602 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 2SCD8Q63PF (NVX-CoV2373 adjuvated lipid nanoparticle) RN - 0 (Immunoglobulin G) RN - 0 (Antibodies, Viral) RN - 0 (Antibodies, Neutralizing) RN - SARS-CoV-2 variants SB - IM MH - Adult MH - Humans MH - *COVID-19/prevention & control MH - SARS-CoV-2 MH - Immunoglobulin G MH - Immunogenicity, Vaccine MH - Antibodies, Viral MH - Antibodies, Neutralizing PMC - PMC10237325 OTO - NOTNLM OT - Booster OT - COVID-19 OT - NVX-CoV2373 OT - SARS-CoV-2 vaccine OT - Vaccine immunogenicity OT - Vaccine safety COIS- Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors are contract or full-time employees of Novavax and as such receive a salary for their work. EDAT- 2023/06/05 00:41 MHDA- 2023/06/21 06:42 PMCR- 2023/06/02 CRDT- 2023/06/04 22:02 PHST- 2023/02/13 00:00 [received] PHST- 2023/05/04 00:00 [revised] PHST- 2023/05/18 00:00 [accepted] PHST- 2023/06/21 06:42 [medline] PHST- 2023/06/05 00:41 [pubmed] PHST- 2023/06/04 22:02 [entrez] PHST- 2023/06/02 00:00 [pmc-release] AID - S0264-410X(23)00612-6 [pii] AID - 10.1016/j.vaccine.2023.05.051 [doi] PST - ppublish SO - Vaccine. 2023 Jun 29;41(29):4280-4286. doi: 10.1016/j.vaccine.2023.05.051. Epub 2023 Jun 2.