Immune response and safety of heterologous ChAdOx1-nCoV-19/mRNA-1273 vaccination compared with homologous ChAdOx1-nCoV-19 or homologous mRNA-1273 vaccination

Wang-Huei Sheng, Sui-Yuan Chang, Pin-Hung Lin, Ming-Ju Hsieh, Hao-Hsiang Chang, Chien-Yu Cheng, Hung-Chih Yang, Ching-Fu Pan, Si-Man Ieong, Tai-Ling Chao, Jang-Pin Chen, Shu-Hsing Cheng, Shan-Chwen Chang, Wang-Huei Sheng, Sui-Yuan Chang, Pin-Hung Lin, Ming-Ju Hsieh, Hao-Hsiang Chang, Chien-Yu Cheng, Hung-Chih Yang, Ching-Fu Pan, Si-Man Ieong, Tai-Ling Chao, Jang-Pin Chen, Shu-Hsing Cheng, Shan-Chwen Chang

Abstract

Background/purpose: Efficacy and safety data of heterologous prime-boost vaccination against SARS-CoV-2 remains limited.

Methods: We recruited adult volunteers for homologous or heterologous prime-boost vaccinations with adenoviral (ChAdOx1, AstraZeneca) and/or mRNA (mRNA-1273, Moderna) vaccines. Four groups of prime-boost vaccination schedules were designed: Group 1, ChAdOx1/ChAdOx1 8 weeks apart; Group 2, ChAdOx1/mRNA-1273 8 weeks apart; Group 3, ChAdOx1/mRNA-1273 4 weeks apart; and Group 4, mRNA-1273/mRNA-1273 4 weeks apart. The primary outcome was serum anti-SARS-CoV-2 IgG titers and neutralizing antibody titers against B.1.1.7 (alpha) and B.1.617.2 (delta) variants on day 28 after the second dose. Adverse events were recorded up until 84 days after the second dose.

Results: We enrolled 399 participants with a median age of 41 years and 75% were female. On day 28 after the second dose, the anti-SARS-CoV-2 IgG titers of both heterologous vaccinations (Group 2 and Group 3) were significantly higher than that of homologous ChAdOx1 vaccination (Group 1), and comparable with homologous mRNA-1273 vaccination (Group 4). The heterologous vaccination group had better neutralizing antibody responses against the alpha and delta variant as compared to the homologous ChAdOx1 group. Most of the adverse events (AEs) were mild and transient. AEs were less frequent when heterologous boosting was done at 8 weeks rather than at 4 weeks.

Conclusion: Heterologous ChAdOx1/mRNA-1273 vaccination provided higher immunogenicity than homologous ChAdOx1 vaccination and comparable immunogenicity with the homologous mRNA-1273 vaccination. Our results support the safety and efficacy of heterologous prime-boost vaccination using the ChAdOx1 and mRNA-1273 COVID-19 vaccines. (ClinicalTrials.gov number, NCT05074368).

Keywords: Adenovirus-vector vaccine; Coronavirus disease 2019 (COVID-19); Immune response; Messenger RNA vaccine; Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2).

Conflict of interest statement

Declaration of competing interest The authors have no conflicts of interest relevant to this article.

Copyright © 2022. Published by Elsevier B.V.

Figures

Figure 1
Figure 1
Classification of four study groups in this study.
Figure 2
Figure 2
SARS-CoV-2 anti-spike IgG responses and spike-specific memory B cell responses after boost dose among four groups. (A) Distributions of SARS-CoV-2 anti-spike IgG responses at the day before and 14th, 28th, and 84th days after boost vaccination; (B) Responses of spike-specific memory B cells at the day before and 28th days after boost dose among four groups. (∗P 

Figure 3

The serum neutralizing antibody titers…

Figure 3

The serum neutralizing antibody titers (NT 50 ) of 4 Groups of study…

Figure 3
The serum neutralizing antibody titers (NT50) of 4 Groups of study subjects against SARS-CoV-2 (A) Alpha variant, and (B) Delta variant.

Figure 4

Immunological response of SARS-CoV-2 spike-specific…

Figure 4

Immunological response of SARS-CoV-2 spike-specific memory T cells before and at 28th day…

Figure 4
Immunological response of SARS-CoV-2 spike-specific memory T cells before and at 28th day post boost vaccination among four groups. Intracellular staining of cytokines in spike-specific CD8+ T cells (A) and spike-specific CD4+ T cells (B). (C) Th1/Th2 cytokine production by T cells using bead-based cytokine assay. (∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.005, ∗∗∗∗P < 0.001).
Figure 3
Figure 3
The serum neutralizing antibody titers (NT50) of 4 Groups of study subjects against SARS-CoV-2 (A) Alpha variant, and (B) Delta variant.
Figure 4
Figure 4
Immunological response of SARS-CoV-2 spike-specific memory T cells before and at 28th day post boost vaccination among four groups. Intracellular staining of cytokines in spike-specific CD8+ T cells (A) and spike-specific CD4+ T cells (B). (C) Th1/Th2 cytokine production by T cells using bead-based cytokine assay. (∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.005, ∗∗∗∗P < 0.001).

References

    1. World Health Organization (WHO) WHO coronavirus (COVID-19) dashboard.
    1. Taiwan Centers for Diseases Control (T-CDC) COVID-19 (SARS-CoV-2 infection)
    1. World Health Organization AZD1222 vaccine against COVID-19 developed by Oxford University and AstraZeneca: background paper.
    1. Voysey M., Costa Clemens S.A., Madhi S.A., Weckx L.Y., Folegatti P.M., Aley P.K., et al. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomized trials. Lancet. 2021;397:881–891.
    1. World Health Organization mRNA-1273 vaccine (Moderna) against COVID-19 background document: draft prepared by the strategic advisory group of experts (SAGE) on immunization working group on COVID-19 vaccines. 19 January 2021.
    1. World Health Organization Interim recommendations for use of the Pfizer-BioNTech COVID-19 vaccine, BNT162b2, under emergency use listing. 15 June 2021.
    1. Pottegard A., Lund L.C., Karlstad O., Dahl J., Andersen M., Hallas J., et al. Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study. Br Med J. 2021;373:n1114.
    1. Greinacher A., Thiele T., Warkentin T.E., Weisser K., Kyrle P.A., Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med. 2021;384:2092–2101.
    1. European Medicines Agency AstraZeneca's COVID-19 vaccine: EMA finds possible link to very rare cases of unusual blood clots with low blood platelets. April 7, 2021. (accessed August 20, 2021)
    1. Hillus D., Schwarz T., Tober-Lau P., Vanshylla K., Hastor H., Thibeault C., et al. Safety, reactogenicity and immunogenicity of homologous and heterologous prime-boost immunization with ChAdOx1-nCoV19 and BNT162b2: a prospective cohort study. Lancet Respir Med. 2021;9:1255–1265.
    1. Normark J., Vikstrom L., Gwon T.D., Persson I.L., Edin A., Bjorsell T., et al. Heterologous ChAdOx1 nCoV-19 and mRNA-1273 vaccination. N Engl J Med. 2021;385:1049–1051.
    1. WHO Guidelines on clinical evaluation of vaccines: regulatory expectations.
    1. WHO AstraZeneca ChAdOx1-S/nCoV-19 [recombinant], COVID-19 vaccine.
    1. Atmar R.L., Lyke K.E., Deming M.E., Jackson L.A., Branche A.R., El Sahly H.M., et al. Homologous and heterologous COVID-19 booster vaccinations. N Engl J Med. 2022 doi: 10.1056/NEJMoa2116414. (Online ahead of print on Jan 26, 2022)
    1. Khoury D.S., Cromer D., Reynaldi A., Schlub T.E., Wheatley A.K., Juno J.A., et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021;27:1205–1211.
    1. Feng S., Phillips D.J., White T., Sayal H., Aley P.K., Bibi S., et al. Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection. Nat Med. 2021;27:2032–2040.
    1. Schmidt T., Klemis V., Schub D., Mihm J., Hielscher F., Marx S., et al. Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination. Nat Med. 2021;27:1530–1535.
    1. Borobia A.M., Carcas A.J., Perez-Olmeda M., Castano L., Bertran M.J., Garcia-Perez J., et al. Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicenter, open-label, randomized, controlled, phase 2 trial. Lancet. 2021;398:121–130.
    1. Barros-Martins J., Hammerschmidt S.I., Cossmann A., Odak I., Stankov M.V., Ramos G.M., et al. Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1nCoV-19/BNT162b2 vaccination. Nat Med. 2021;27:1525–1529.
    1. Grob R., Zanoni M., Seidel A., Conzelmann C., Gilg A., Krnavek D., et al. Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants. EBioMedicine. 2022;75:103761.
    1. Pozzetto B., Legros V., Djebali S., Barateau V., Guiber N., Villard M., et al. Immunogenicity and efficacy of heterologous ChadOx1/BNT162b2 vaccination. Nature. 2021;600:701–706.
    1. Shaw R.H., Stuart A., Greenland M., Liu X., Nguyen Van-Tam J.S., Snape M.D., Com-COV Study Group Heterologous prime-boost COVID-19 vaccination: initial reactogenicity data. Lancet. 2021;397:2043–2046.
    1. Parry H., Bruton R., Stephens C., Brown K., Amirthalingam G., Hallis B., et al. Extended interval BNT162b2 vaccination enhances peak antibody generation in older people. medRxiv. 2021 doi: 10.1101/2021.05.15.21257017. (Published online May 15) (Preprint)

Source: PubMed

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