Equal Maintenance of Anti-SARS-CoV-2 Antibody Levels Induced by Heterologous and Homologous Regimens of the BNT162b2, ChAdOx1, CoronaVac and Ad26.COV2.S Vaccines: A Longitudinal Study Up to the 4th Dose of Booster

Several technological approaches have been used to develop vaccines against COVID-19, including those based on inactivated viruses, viral vectors, and mRNA. This study aimed to monitor the maintenance of anti-SARS-CoV-2 antibodies in individuals from Brazil according to the primary vaccination regimen, as follows: BNT162b2 (group 1; 22) and ChAdOx1 (group 2; 18). Everyone received BNT162b2 in the first booster while in the second booster CoronaVac, Ad26.COV2.S, or BNT162b2. Blood samples were collected from 2021 to 2023 to analyze specific RBD (ELISA) and neutralizing antibodies (PRNT50). We observed a progressive increase in anti-RBD and neutralizing antibodies in each subsequent dose, remaining at high titers until the end of follow-up. Group 1 had higher anti-RBD antibody titers than group 2 after beginning the primary regimen, with significant differences after the 2nd and 3rd doses. Group 2 showed a more expressive increase after the first booster with BNT162B2 (heterologous booster). Group 2 also presented high levels of neutralizing antibodies against the Gamma and Delta variants until five months after the second booster. In conclusion, the circulating levels of anti-RBD and neutralizing antibodies against the two variants of SARS-CoV-2 were durable even five months after the 4th dose, suggesting that periodic booster vaccinations (homologous or heterologous) induced long-lasting immunity.

References

Lv J, Wu H, Xu J, Liu J . Immunogenicity and safety of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine: a systematic review. Infect Dis Poverty. 2022; 11(1):53. PMC: 9100319. DOI: 10.1186/s40249-022-00977-x. View

Beavis K, Matushek S, Abeleda A, Bethel C, Hunt C, Gillen S . Evaluation of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies. J Clin Virol. 2020; 129:104468. PMC: 7255182. DOI: 10.1016/j.jcv.2020.104468. View

Deng J, Ma Y, Liu Q, Du M, Liu M, Liu J . Comparison of the Effectiveness and Safety of Heterologous Booster Doses with Homologous Booster Doses for SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2022; 19(17). PMC: 9517782. DOI: 10.3390/ijerph191710752. View

Clemens S, Marchevsky N, Kelly S, Felle S, Eldawi A, Rajasingam R . Immunogenicity, safety and reactogenicity of heterologous (third dose) booster vaccination with a full or fractional dose of two different COVID-19 vaccines: A phase 4, single-blind, randomized controlled trial in adults. Hum Vaccin Immunother. 2023; 19(2):2233400. PMC: 10348030. DOI: 10.1080/21645515.2023.2233400. View

Roehrig J, Hombach J, Barrett A . Guidelines for Plaque-Reduction Neutralization Testing of Human Antibodies to Dengue Viruses. Viral Immunol. 2008; 21(2):123-32. DOI: 10.1089/vim.2008.0007. View

Ita K . Coronavirus Disease (COVID-19): Current Status and Prospects for Drug and Vaccine Development. Arch Med Res. 2020; 52(1):15-24. PMC: 7832760. DOI: 10.1016/j.arcmed.2020.09.010. View

Volpe G, Vessoni S, Soares L, Almeida M, Braga P, de Moraes G . Antibody response dynamics to CoronaVac vaccine and booster immunization in adults and the elderly: A long-term, longitudinal prospective study. IJID Reg. 2023; 7:222-229. PMC: 10076246. DOI: 10.1016/j.ijregi.2023.04.003. View

Fadlyana E, Setiabudi D, Kartasasmita C, Putri N, Hadinegoro S, Mulholland K . Immunogenicity and safety in healthy adults of full dose versus half doses of COVID-19 vaccine (ChAdOx1-S or BNT162b2) or full-dose CoronaVac administered as a booster dose after priming with CoronaVac: a randomised, observer-masked, controlled.... Lancet Infect Dis. 2023; 23(5):545-555. DOI: 10.1016/S1473-3099(22)00800-3. View

Liu X, Munro A, Wright A, Feng S, Janani L, Aley P . Persistence of immune responses after heterologous and homologous third COVID-19 vaccine dose schedules in the UK: eight-month analyses of the COV-BOOST trial. J Infect. 2023; 87(1):18-26. PMC: 10116128. DOI: 10.1016/j.jinf.2023.04.012. View

10.

Khaleeq S, Sengupta N, Kumar S, Patel U, Rajmani R, Reddy P . Neutralizing Efficacy of Encapsulin Nanoparticles against SARS-CoV2 Variants of Concern. Viruses. 2023; 15(2). PMC: 9961482. DOI: 10.3390/v15020346. View

11.

Taniguchi Y, Suemori K, Tanaka K, Okamoto A, Murakami A, Miyamoto H . Long-term transition of antibody titers in healthcare workers following the first to fourth doses of mRNA COVID-19 vaccine: Comparison of two automated SARS-CoV-2 immunoassays. J Infect Chemother. 2023; 29(5):534-538. PMC: 9867842. DOI: 10.1016/j.jiac.2023.01.007. View

12.

de Oliveira C, Neto W, da Silva C, Ribeiro A, Martins L, de Sousa A . Absence of Anti-RBD Antibodies in SARS-CoV-2 Infected or Naive Individuals Prior to Vaccination with CoronaVac Leads to Short Protection of Only Four Months Duration. Vaccines (Basel). 2022; 10(5). PMC: 9147084. DOI: 10.3390/vaccines10050690. View

13.

Padhi A, Tripathi T . Can SARS-CoV-2 Accumulate Mutations in the S-Protein to Increase Pathogenicity?. ACS Pharmacol Transl Sci. 2020; 3(5):1023-1026. PMC: 7551720. DOI: 10.1021/acsptsci.0c00113. View

14.

Goel R, Painter M, Apostolidis S, Mathew D, Meng W, Rosenfeld A . mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern. Science. 2021; 374(6572):abm0829. PMC: 9284784. DOI: 10.1126/science.abm0829. View

15.

Clemens S, Weckx L, Clemens R, Mendes A, Ramos Souza A, Silveira M . Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study. Lancet. 2022; 399(10324):521-529. PMC: 8782575. DOI: 10.1016/S0140-6736(22)00094-0. View

16.

Raskin S . Genetics of COVID-19. J Pediatr (Rio J). 2020; 97(4):378-386. PMC: 7539923. DOI: 10.1016/j.jped.2020.09.002. View

17.

Lu R, Zhao X, Li J, Niu P, Yang B, Wu H . Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395(10224):565-574. PMC: 7159086. DOI: 10.1016/S0140-6736(20)30251-8. View

18.

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

19.

Wietschel K, Fechtner K, Antileo E, Abdurrahman G, Drechsler C, Makuvise M . Non-cross-reactive epitopes dominate the humoral immune response to COVID-19 vaccination - kinetics of plasma antibodies, plasmablasts and memory B cells. Front Immunol. 2024; 15:1382911. PMC: 11130424. DOI: 10.3389/fimmu.2024.1382911. View

20.

Long Q, Tang X, Shi Q, Li Q, Deng H, Yuan J . Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med. 2020; 26(8):1200-1204. DOI: 10.1038/s41591-020-0965-6. View