Safety and Immunogenicity of a Third Dose of COVID-19 Protein Subunit Vaccine (Covovax) After Homologous and Heterologous Two-dose Regimens

Objectives: To report the safety and immunogenicity profile of a protein subunit vaccine (Covovax) given as a third (booster) dose to individuals primed with different primary vaccine regimens.

Methods: A third dose was administered to individuals with an interval range of 3-10 months after the second dose. The four groups were classified according to their primary vaccine regimens, including two-dose BBIBP-CorV, AZD1222, BNT162b2, and CoronaVac/AZD1222. Immunogenicity analysis was performed to determine binding antibodies, neutralizing activity, and the T-cell responses.

Results: Overall, 210 individuals were enrolled and boosted with the Covovax vaccine. The reactogenicity was mild to moderate. Most participants elicited a high level of binding and neutralizing antibody against Wild-type and Omicron variants after the booster dose. In participants who were antinucleocapsid immunoglobulin G-negative from all groups, a booster dose could elicit neutralizing activity to Wild-type and Omicron variants by more than 95% and 70% inhibition at 28 days, respectively. The Covovax vaccine could elicit a cell-mediated immune response.

Conclusion: The protein subunit vaccine (Covovax) can be proposed as a booster dose after two different priming dose regimens. It has strong immunogenicity and good safety profiles.

Citing Articles

Immunogenicity and Safety of SARS-CoV-2 Protein Subunit Recombinant Vaccine (IndoVac) as a Booster Dose against COVID-19 in Indonesian Adults.

Rusmil K, Fadlyana E, Girsang R, Adrizain R, Rahmadi A, Suryadinata H Vaccines (Basel). 2024; 12(5).

PMID: 38793791 PMC: 11125677. DOI: 10.3390/vaccines12050540.

Editorial: COVID-19 booster vaccination: increasing immunity against life-threatening infection.

Yorsaeng R, Atsawawaranunt K, Riad A Front Public Health. 2024; 11:1342118.

PMID: 38264241 PMC: 10804992. DOI: 10.3389/fpubh.2023.1342118.

Structural understanding of SARS-CoV-2 virus entry to host cells.

Le K, Kannappan S, Kim T, Lee J, Lee H, Kim K Front Mol Biosci. 2023; 10:1288686.

PMID: 38033388 PMC: 10683510. DOI: 10.3389/fmolb.2023.1288686.

Real-World Study: Hybrid Immunity against SARS-CoV-2 Influences the Antibody Levels and Persistency Lasting More than One Year.

Kanokudom S, Chansaenroj J, Assawakosri S, Suntronwong N, Yorsaeng R, Wongsrisang L Vaccines (Basel). 2023; 11(11).

PMID: 38006025 PMC: 10674428. DOI: 10.3390/vaccines11111693.

Immunogenicity of NVX-CoV2373 heterologous boost against SARS-CoV-2 variants.

Lyke K, Atmar R, Dominguez Islas C, Posavad C, Deming M, Branche A NPJ Vaccines. 2023; 8(1):98.

PMID: 37433788 PMC: 10336079. DOI: 10.1038/s41541-023-00693-z.

References

Assawakosri S, Kanokudom S, Chansaenroj J, Suntronwong N, Auphimai C, Nilyanimit P . Persistence of immunity against Omicron BA.1 and BA.2 variants following homologous and heterologous COVID-19 booster vaccines in healthy adults after a two-dose AZD1222 vaccination. Int J Infect Dis. 2022; 122:793-801. PMC: 9293855. DOI: 10.1016/j.ijid.2022.07.038. View

Munro A, Janani L, Cornelius V, Aley P, Babbage G, Baxter D . Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial. Lancet. 2021; 398(10318):2258-2276. PMC: 8639161. DOI: 10.1016/S0140-6736(21)02717-3. View

Mallory R, Formica N, Pfeiffer S, Wilkinson B, Marcheschi A, Albert G . Safety and immunogenicity following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373): a secondary analysis of a randomised, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2022; 22(11):1565-1576. PMC: 9365313. DOI: 10.1016/S1473-3099(22)00420-0. View

Moghnieh R, El Hajj C, Abdallah D, Jbeily N, Bizri A, Sayegh M . Immunogenicity and Effectiveness of Primary and Booster Vaccine Combination Strategies during Periods of SARS-CoV-2 Delta and Omicron Variants. Vaccines (Basel). 2022; 10(10). PMC: 9607825. DOI: 10.3390/vaccines10101596. View

Viana R, Moyo S, Amoako D, Tegally H, Scheepers C, Althaus C . Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa. Nature. 2022; 603(7902):679-686. PMC: 8942855. DOI: 10.1038/s41586-022-04411-y. View

Assawakosri S, Kanokudom S, Suntronwong N, Auphimai C, Nilyanimit P, Vichaiwattana P . Neutralizing Activities Against the Omicron Variant After a Heterologous Booster in Healthy Adults Receiving Two Doses of CoronaVac Vaccination. J Infect Dis. 2022; 226(8):1372-1381. DOI: 10.1093/infdis/jiac092. View

Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S . Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. N Engl J Med. 2020; 383(24):2320-2332. PMC: 7494251. DOI: 10.1056/NEJMoa2026920. View

Ai J, Zhang Y, Zhang H, Zhang Q, Fu Z, Lin K . Safety and immunogenicity of a third-dose homologous BBIBP-CorV boosting vaccination: interim results from a prospective open-label study. Emerg Microbes Infect. 2022; 11(1):639-647. PMC: 8881062. DOI: 10.1080/22221751.2022.2025746. View

Bhiman J, Richardson S, Lambson B, Kgagudi P, Mzindle N, Kaldine H . Novavax NVX-COV2373 triggers neutralization of Omicron sub-lineages. Sci Rep. 2023; 13(1):1222. PMC: 9867547. DOI: 10.1038/s41598-023-27698-x. View

10.

Shinde V, Bhikha S, Hoosain Z, Archary M, Bhorat Q, Fairlie L . Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant. N Engl J Med. 2021; 384(20):1899-1909. PMC: 8091623. DOI: 10.1056/NEJMoa2103055. View

11.

Tian J, Patel N, Haupt R, Zhou H, Weston S, Hammond H . SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nat Commun. 2021; 12(1):372. PMC: 7809486. DOI: 10.1038/s41467-020-20653-8. View

12.

Kuhlmann C, Mayer C, Claassen M, Maponga T, Burgers W, Keeton R . Breakthrough infections with SARS-CoV-2 omicron despite mRNA vaccine booster dose. Lancet. 2022; 399(10325):625-626. PMC: 8765759. DOI: 10.1016/S0140-6736(22)00090-3. View

13.

Kanokudom S, Assawakosri S, Suntronwong N, Auphimai C, Nilyanimit P, Vichaiwattana P . Safety and Immunogenicity of the Third Booster Dose with Inactivated, Viral Vector, and mRNA COVID-19 Vaccines in Fully Immunized Healthy Adults with Inactivated Vaccine. Vaccines (Basel). 2022; 10(1). PMC: 8779615. DOI: 10.3390/vaccines10010086. View

14.

Cele S, Jackson L, Khoury D, Khan K, Moyo-Gwete T, Tegally H . Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization. Nature. 2022; 602(7898):654-656. PMC: 8866126. DOI: 10.1038/s41586-021-04387-1. View

15.

Busa R, Sorrentino M, Russelli G, Amico G, Miceli V, Miele M . Specific Anti-SARS-CoV-2 Humoral and Cellular Immune Responses After Booster Dose of BNT162b2 Pfizer-BioNTech mRNA-Based Vaccine: Integrated Study of Adaptive Immune System Components. Front Immunol. 2022; 13:856657. PMC: 8987231. DOI: 10.3389/fimmu.2022.856657. View

16.

Zuo F, Abolhassani H, Du L, Piralla A, Bertoglio F, de Campos-Mata L . Heterologous immunization with inactivated vaccine followed by mRNA-booster elicits strong immunity against SARS-CoV-2 Omicron variant. Nat Commun. 2022; 13(1):2670. PMC: 9106736. DOI: 10.1038/s41467-022-30340-5. View

17.

Heath P, Galiza E, Baxter D, Boffito M, Browne D, Burns F . Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine. N Engl J Med. 2021; 385(13):1172-1183. PMC: 8262625. DOI: 10.1056/NEJMoa2107659. View

18.

Liu X, Shaw R, Stuart A, Greenland M, Aley P, Andrews N . Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial. Lancet. 2021; 398(10303):856-869. PMC: 8346248. DOI: 10.1016/S0140-6736(21)01694-9. View

19.

Kanokudom S, Assawakosri S, Suntronwong N, Chansaenroj J, Auphimai C, Nilyanimit P . Comparison of the reactogenicity and immunogenicity of a reduced and standard booster dose of the mRNA COVID-19 vaccine in healthy adults after two doses of inactivated vaccine. Vaccine. 2022; 40(39):5657-5663. PMC: 9393164. DOI: 10.1016/j.vaccine.2022.08.033. View

20.

Tande A, Pollock B, Shah N, Farrugia G, Virk A, Swift M . Impact of the Coronavirus Disease 2019 (COVID-19) Vaccine on Asymptomatic Infection Among Patients Undergoing Preprocedural COVID-19 Molecular Screening. Clin Infect Dis. 2021; 74(1):59-65. PMC: 7989519. DOI: 10.1093/cid/ciab229. View