Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan:126:64-72.
doi: 10.1016/j.ijid.2022.11.022. Epub 2022 Nov 22.

Safety and immunogenicity of a third dose of COVID-19 protein subunit vaccine (CovovaxTM) after homologous and heterologous two-dose regimens

Sitthichai Kanokudom  1 , Jira Chansaenroj  2 , Nungruthai Suntronwong  2 , Suvichada Assawakosri  1 , Ritthideach Yorsaeng  2 , Pornjarim Nilyanimit  2 , Ratchadawan Aeemjinda  2 , Nongkanok Khanarat  2 , Preeyaporn Vichaiwattana  2 , Sirapa Klinfueng  2 , Thanunrat Thongmee  2 , Apirat Katanyutanon  3 , Wichai Thanasopon  3 , Jirawan Arayapong  4 , Withak Withaksabut  3 , Donchida Srimuan  2 , Thaksaporn Thatsanatorn  2 , Natthinee Sudhinaraset  2 , Nasamon Wanlapakorn  2 , Sittisak Honsawek  5 , Yong Poovorawan  6
Affiliations

Safety and immunogenicity of a third dose of COVID-19 protein subunit vaccine (CovovaxTM) after homologous and heterologous two-dose regimens

Sitthichai Kanokudom et al. Int J Infect Dis. 2023 Jan.

Abstract

Objectives: To report the safety and immunogenicity profile of a protein subunit vaccine (CovovaxTM) 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 CovovaxTM 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 CovovaxTM vaccine could elicit a cell-mediated immune response.

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

Keywords: Booster dose; Covovax(TM); Novavax; Omicron; SARS-CoV-2; Side effect.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The authors have no competing interests to declare.

Figures

Fig. 1
Fig. 1
Study flow diagram of participant enrollment, blood sampling, and participant categorization. Participants who were primed with two doses of vaccines including SPC, AZC, PFC, and SAC at 3-10 months prior were enrolled to receive the protein subunit vaccine (CovovaxTM) as a booster dose. Blood samples were collected on days 0, 14 (± 7) and 28 (± 7) postbooster vaccination. The participants were categorized for further analysis according to the anti-N IgG titers. Only seronegative anti-N IgG participants were eligible for evaluation of immunogenicity analyses after booster vaccination. The 12 exclude for analysis (¶) including 10 lost to follow-up and two outliners. The dotted boxes indicate the participants after categorization using anti-N IgG. Abbreviations: AZC, AZD1222; Ig, immunoglobulin; Inf, infection; N, nucleocapsid; neg, negative; PFC, BNT162b2; pos, positive; SAC, CoronaVac/AZD1222; SPC, BBIBP-CorV.
Fig. 2
Fig. 2
Local, systemic, and adverse events of total participants experienced 7 days after receiving of a protein subunit vaccine.
Fig. 3
Fig. 3
The anti-RBD Ig/IgG responses of the enrolled participants. Sera samples of SPC, AZC, PFC, and SAC groups were monitored at 0, 14 and 28 days. (a) anti-RBD Ig (U/ml) and (b) anti-RBD IgG (BAU/ml) of the total enrolled participants. (c) anti-RBD Ig (U/ml) and (d) anti-RBD IgG (BAU/ml) of the seronegative anti-N IgG participants. The gray area indicates the seronegativity of the anti-RBD Ig (<0.8 U/ml) or anti-RBG IgG (<7.1 BAU/ml). The lines represent GMTs (95% CIs). A pairwise comparisons display (GMR) and significant values including P <0.05 (*), P <0.001 (**), P <0.001 (***). Abbreviations: AZC, AZD1222; BAU, binding antibody units; CIs, confidence intervals; GMT, geometric mean titer; GMR, geometric mean ratio; Ig, immunoglobulin; N, nucleocapsid; ns, no statistical significance; PFC, BNT162b2; SAC, CoronaVac/AZD1222; SPC, BBIBP-CorV.
Fig. 4
Fig. 4
Comparison of individual anti-RBD Ig values stratified by anti-N IgG titers. Participants were classified by seronegative and seropositive anti-N IgG (cut-off ≥ 1.4 S/C) before a booster dose. (a) SPC, (b) AZC, (c) PFC, (d) SAC regimens. The gray area indicates the seronegativity of the anti-RBD Ig (<0.8 U/ml). The lines represent GMTs (95% CI). A pairwise comparisons display GMR and significant values including P <0.001 (**). Abbreviations: AZC, AZD1222; CIs, confidence intervals; GMT, geometric mean titer; GMR, geometric mean ratio; Ig, immunoglobulin; N, nucleocapsid; ns, no statistical significance; PFC, BNT162b2; RBD, recptor binding domain; SAC, CoronaVac/AZD1222; SPC, BBIBP-CorV.
Fig. 5
Fig. 5
Neutralizing activity of participants against the Wild-type SARS-CoV-2 virus (a) and BA.2 Omicron variant (b). Lines represent the median (interquartile range [IQR]). The gray area indicates the seronegativity of neutralizing activity of the Wild-type (<35%) and BA.2 Omicron variant (<30%). Abbreviations: AZC, AZD1222; PFC, BNT162b2; SAC, CoronaVac/AZD1222; SPC, BBIBP-CorV.
Fig. 6
Fig. 6
IFN-γ release assay. Whole blood samples from the participants were heparinized and then transferred to the Antigen 3-QuantiFERON blood collection tube for 21 hours. The IFN-γ release was monitored by enzyme-linked immunosorbent assay. Lines represent the median (interquartile range). A pairwise comparisons display significant values including P <0.001 (***). Abbreviations: AZC, AZD1222; IFN, interferon; PFC, BNT162b2; SAC, CoronaVac/AZD1222; SPC, BBIBP-CorV.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ai J, Zhang Y, Zhang H, Zhang Q, Fu Z, Lin K, et al. Safety and immunogenicity of a third-dose homologous BBIBP-CorV boosting vaccination: interim results from a prospective open-label study. Emerg Microbes Infect. 2022;11:639–647. - PMC - PubMed
    1. Assawakosri S, Kanokudom S, Chansaenroj J, Suntronwong N, Auphimai C, Nilyanimit P, et al. 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 - PubMed
    1. Assawakosri S, Kanokudom S, Suntronwong N, Auphimai C, Nilyanimit P, Vichaiwattana P, et al. Neutralizing activities against the omicron variant after a heterologous booster in healthy adults receiving two doses of CoronaVac vaccination. J Infect Dis. 2022;226:1372–1381. - PubMed
    1. Bhiman JN, Richardson SI, Lambson BE, Kgagudi P, Mzindle N, Kaldine H, et al. Novavax NVX-COV2373 triggers potent neutralization of Omicron sub-lineages. bioRxiv. 2022 - PMC - PubMed

    2. https://www.biorxiv.org/content/10.1101/2022.07.14.500148v1. [Accessed 17 July 2022].

    1. Busà R, Sorrentino MC, Russelli G, Amico G, Miceli V, Miele M, et al. 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 - PMC - PubMed

Supplementary concepts