Heterologous vaccination of BNT162b2 in Ad26. COV2.S-vaccinated healthcare workers elicits long-term humoral immune response

Authors

  • B Jacobson Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Medicine and National Health Laboratory Service, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Afric
  • A Khan Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
  • AH Shulman Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
  • B Segal Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
  • E Mayne 3 Clinical Laboratory Services, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Division of Immunology, Faculty of Health Sciences, University of Cape Town, South Africa
  • L-G Bekker Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa
  • I Sanne Clinical HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg
  • G Gray South African Medical Research Council, Cape Town, South Africa

DOI:

https://doi.org/10.7196/SAMJ.2022.v112.i11.16614

Keywords:

COV2, Vaccine, RNA Virus

Abstract

Background. To date, there are no immunological data for the SARS-CoV-2 heterologous vaccination schedule in the South African (SA) population.
Objectives. To assess and compare the immunogenicity and reactogenicity of the Jansen Ad26.COV2.S vaccine with the Pfizer/BioNTechBNT162b2 booster following prime Ad26.COV2.S in 65 SA healthcare workers.
Methods. In a prospective, quantitative, cross-sectional trial on individuals >18 years of age vaccinated with a single Ad26.COV2.S dose or single Ad26.COV2.S and a BNT162b2 single-dose/both doses booster, participants filled in a questionnaire on their demographics, type of vaccination, breakthrough infection/s (BTI/s), vaccine reactogenicity, prior SARS-CoV-2 infection and dates of vaccination. Qualitative analysis for presence/absence of anti-S (spike) immunoglobulin G (IgG) was performed using the Euroimmun anti-IgG enzyme-linked immunoassay kit, and anti-S IgG titres were quantitatively assessed using the Abbott IgG Quant II kit.
Results. Between 28 October 2021 and 30 November 2021, 65 individuals were enrolled and assigned as either prime Ad26.COV2.S (n=18) or Ad26.COV2.S with a BNT162b2 supplement (n=47) at Charlotte Maxeke Johannesburg Academic Hospital, SA (mean age 45 years (95% confidence interval (CI) 29.5 - 58), 42 women (64.6%) and 23 men (35.4%)). The median IgG titre for the primed Ad26.COV2.S group was 4 272.55 (95% CI 68.40 - 10 351.40) and that for the BNT162b2 supplement group was 7 360.80 (95% CI 4 207.40 - 15 372.60). In the univariate model, the BNT162b2 supplement group showed a significant 1.99 times higher antibody titre factor (95% CI 0.045 - 5.553; p<0.005) than the Ad26.COV2.S group. In both univariate and multivariate models, age, time since prime vaccination, BTI and prior infection failed to show any statistically significant association (p>0.05) with antibody titres in both groups. However, sex (–55.381 (95% CI –76.984 - –13.498; p=0.018) in a multivariate model was found to have a statistically significant association with anti-S IgG titres observed in both groups. Participants who received their first dose of BNT162b2 9 - 10 months after their prime Ad26.COV2.S (n=44) had a higher degree of antibody response than those who received it earlier. Reactogenicity was observed to be manageable, with mild/moderate adverse effects in the study population.
Conclusion. A BNT162b2 supplement given in single or two doses as booster in individuals primed with Ad26.COV2.S induced
immunological response, with acceptable and manageable reactogenicity. This study provides novel evidence of the highest degree of antibody response in individuals who received a BNT162b2 first dose 9 - 10 months after prime Ad26.COV2.S, implying that a longer time gap between the two vaccines stimulates higher antibody response than a shorter gap, and that this antibody response can persist for as long as 6 months after the last BNT162b2 dose.

References

Kim D, Lee JY, Yang JS, Kim JW, Kim VN, Chang H. The architecture of SARS-CoV-2 transcriptome. Cell 2020;181(4):914-921.e10. https://doi.org/10.1016/j.cell.2020.04.011

Monteil V, Kwon H, Prado P, et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 2020;181(4):905-913.e7. https://doi.org/10.1016/j.cell.2020.04.004

Mercurio I, Tragni V, Busto F, de Grassi A, Pierri CL. Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: From conformational changes to novel neutralizing antibodies. Cell Mol Life Sci 2021;78(4):1501-1522. https://doi.org/10.1007/s00018-020-03580-1

Changrob S, Fu Y, Guthmiller JJ, Halfmann PJ, et al. Cross-neutralisation of emerging SARS-CoV-2 variants of concern by antibodies targeting distinct epitopes on spike. mBio 2021;12(6):e0297521. https://doi.org/10.1128/mBio.02975-21

Mohammadi M, Shayestehpour M, Mirzaei H. The impact of spike mutated variants of SARS-CoV2 [Alpha, Beta, Gamma, Delta, and Lambda] on the efficacy of subunit recombinant vaccines. Braz J Infect Dis 2021;25(4):101606. https://doi.org/10.1016/j.bjid.2021.101606

McCormick KD, Jacobs JL, Mellors JW. The emerging plasticity of SARS-CoV-2. Science 2021;371(6536):1306-1308. https://doi.org/10.1126/science.abg4493

COG-UK. COG-UK report on SARS-CoV-2 spike mutations of interest in the UK. 15 January 2021. https://www.cogconsortium.uk/wp-content/uploads/2021/01/Report-2_COG-UK_SARS-CoV-2-Mutations.pdf (accessed 28 February 2022).

Ball P. The lightning-fast quest for COVID vaccines – and what it means for other diseases. Nature 2021;589(7840):16-18. https://doi.org/10.1038/d41586-020-03626-1

Sadoff J, Gray G, Vandebosch A, et al.; ENSEMBLE Study Group. Safety and efficacy of singledose Ad26.COV2.S vaccine against Covid-19. N Engl J Med 2021;384(23):2187-2201. https://doi.org/10.1056/NEJMoa2101544

Gededzha MP, Mampeule N, Jugwanth S, et al. Performance of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies in South Africa. PLoS ONE 2021;16(6):e0252317. https://doi.org/10.1371/journal.pone.0252317

Champely S. Pwr: Basic functions for power analysis, 2020. https://CRAN.R-project.org/package=pwr (accessed 3 March 2022).

Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Hillsdale, NJ: L Erlbaum Associates, 1988.

R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing, 2021. https://www.R-project.org/ (accessed 3 March 2022).

Yoshida K, Alexander B. Tableone: Create ‘Table 1’ to describe baseline characteristics with or without propensity score weights. 2021. https://CRAN.R-project.org/package=tableone (accessed 3 March 2022).

Liu X, Shaw RH, Stuart ASV, et al.; Com-COV Study Group. 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. https://doi.org/10.1016/S0140-6736(21)01694-9

Chiu NC, Chi H, Tu YK, et al. To mix or not to mix? A rapid systematic review of heterologous primeboost covid-19 vaccination. Expert Rev Vaccines 2021;20(10):1211-1220. https://doi.org/10.1080/14760584.2021.1971522

Atmar RL, Lyke KE, Deming ME, et al.; DMID 21-0012 Study Group. Homologous and heterologous Covid-19 booster vaccinations. N Engl J Med 2022;386(11):1046-1057. https://doi.org/10.1056/NEJMoa2116414

Khoo NKH, Lim JME, Gill US, et al. Differential immunogenicity of homologous versus heterologous boost in Ad26.COV2.S vaccine recipients. Med (N Y) 2022;3(2):104-118.e4. https://doi.org/10.1016/j.medj.2021.12.004

Borobia AM, Carcas AJ, Pérez-Olmeda M, et al.; CombiVacS Study Group. Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): A multicentre, open-label, randomised, controlled, phase 2 trial. Lancet 2021;398(10295):121-130. https://doi.org/10.1016/S0140-6736(21)01420-3 (erratum in: Lancet 2021;398(10300):582).

Lopez Bernal J, Andrews N, Gower C, et al. Effectiveness of Covid-19 vaccines against the B.1.617.2 (delta) variant. N Engl J Med 2021;385(7):585-594. https://doi.org/10.1056/NEJMoa2108891

Fenwick C, Croxatto A, Coste AT, et al. Changes in SARS-CoV-2 spike versus nucleoprotein antibody responses impact the estimates of infections in population-based seroprevalence studies. J Virol 2021;95(3):e01828-20. https://doi.org/10.1128/JVI.01828-20

Wheeler SE, Shurin GV, Yost M, et al. Differential antibody response to mRNA COVID-19 vaccines in healthy subjects. Microbiol Spectr 2021;9(1):e0034121. https://doi.org/10.1128/Spectrum.00341-21

Tsukinoki K, Yamamoto T, Handa K, et al. Detection of cross-reactive immunoglobulin A against the severe acute respiratory syndrome-coronavirus-2 spike 1 subunit in saliva. PLoS ONE 2021;16(11):e0249979. https://doi.org/0.1371/journal.pone.0249979

Zurac S, Nichita L, Mateescu B, et al. COVID‑19 vaccination and IgG and IgA antibody dynamics in health care workers. Mol Med Rep 2021;24(2):578. https://doi.org/10.3892/mmr.2021.12217

Wisnewski AV, Campillo Luna J, Redlich CA. Human IgG and IgA responses to COVID-19 mRNA vaccines. PLoS ONE 2021;16(6):e0249499. https://doi.org/10.1371/journal.pone.0249499

Harvey RA, Rassen JA, Kabelac CA, et al. Association of SARS-CoV-2 seropositive antibody test with risk of future infection. JAMA Intern Med 2021;181(5):672-679. https://doi.org/10.1001/jamainternmed.2021.0366

Sahin U, Muik A, Derhovanessian E, et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature 2020;586(7830):594-599. https://doi.org/10.1038/s41586-020-2814-7 (erratum in: Nature 2021;590(7844):E17).

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Published

2022-09-21

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Section

Research

How to Cite

1.
Jacobson B, Khan A, Shulman A, Segal B, Mayne E, Bekker L-G, et al. Heterologous vaccination of BNT162b2 in Ad26. COV2.S-vaccinated healthcare workers elicits long-term humoral immune response. S Afr Med J [Internet]. 2022 Sep. 21 [cited 2025 Oct. 7];112(10):828-37. Available from: https://samajournals.co.za/index.php/samj/article/view/184

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