Immunogenicity and safety of heterologous versus homologous prime-boost schedules with inactivated and adenoviral vectored SARS-CoV-2 vaccines - A prospective multi-center study

Pawat Phuensan; Jarongkorn Sirimongkolkasem; Terapong Tantawichien; Jeerath Phannajit; Stephen J Kerr; Pokrath Hansasuta; Prawat Chantharit; Adisorn Wongsa; Pusit Fuengfoo; Anutra Chittinandana; Kriengsak Vareesangthip; Methee Chayakulkeeree; Sureeporn Jangsirikul; Araya Schmidt; Kanyika Wanvimonsuk; Poramed Winichakoon; Rattagan Kajeekul; Wichai Prayoonwiwat; Rungsun Rerknimitr

doi:10.1016/j.heliyon.2023.e23246

Immunogenicity and safety of heterologous versus homologous prime-boost schedules with inactivated and adenoviral vectored SARS-CoV-2 vaccines - A prospective multi-center study

Heliyon. 2023 Dec 3;10(1):e23246. doi: 10.1016/j.heliyon.2023.e23246. eCollection 2024 Jan 15.

Authors

Pawat Phuensan^{1

2}, Jarongkorn Sirimongkolkasem^{1

3}, Terapong Tantawichien², Jeerath Phannajit⁴, Stephen J Kerr⁵, Pokrath Hansasuta⁶, Prawat Chantharit⁷, Adisorn Wongsa⁸, Pusit Fuengfoo⁹, Anutra Chittinandana¹⁰, Kriengsak Vareesangthip¹¹, Methee Chayakulkeeree¹², Sureeporn Jangsirikul^{3

13}, Araya Schmidt¹³, Kanyika Wanvimonsuk¹⁴, Poramed Winichakoon¹⁵, Rattagan Kajeekul¹⁶, Wichai Prayoonwiwat¹⁷, Rungsun Rerknimitr³

Affiliations

¹ Division of Hospital and Ambulatory Medicine, Department of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society and Faculty of Medicine, Chulalongkorn University, Thailand.
² Division of Infectious Diseases, Department of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society and Faculty of Medicine, Chulalongkorn University, Thailand.
³ Division of Gastroenterology, Department of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society and Faculty of Medicine, Chulalongkorn University, Thailand.
⁴ Division of Clinical Epidemiology, Department of Medicine, King Chulalongkorn Memorial Hospital, Thailand.
⁵ Department of Research Affairs, Faculty of Medicine, Chulalongkorn University, Thailand.
⁶ Division of Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Thailand.
⁷ Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Thailand.
⁸ Division of Pulmonary and Critical Care, Department of Medicine, Phramongkutklao Hospital, Thailand.
⁹ Department of Surgery, Phramongkutklao Hospital, Thailand.
¹⁰ Division of Nephrology, Department of Medicine, Bhumibol Adulyadej Hospital, Thailand.
¹¹ Renal Division, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand.
¹² Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Thailand.
¹³ Gastroenterology and Liver Center, MedPark Hospital, Thailand.
¹⁴ Department of Trauma and Emergency Medicine, Royal Thai Airforce Hospital (Sikan), Thailand.
¹⁵ Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Thailand.
¹⁶ Division of Infectious Diseases, Department of Medicine, Maharat Nakhon Ratchasima Hospital, Thailand.
¹⁷ Division of Hematology, Department of Medicine, Phramongkutklao Hospital, Thailand.

Abstract

Background: During the peak of Coronavirus disease (COVID-19) pandemic in Thailand when the emergence of delta variant reduced the efficacy of inactivated vaccine, Thailand had abundance of inactivated vaccine but mRNA vaccine was not available and the supply of adenoviral-vectored vaccine was limited. The heterologous vaccination using CoronaVac and ChAdOx1-nCoV-19 vaccines was applied. We aim to compare the immunogenicity of immune response of primary vaccination with homologous ChAdOx1 nCoV-19 and heterologous vaccination with CoronaVac and ChAdOx1 nCoV-19.

Methods: A total of 430 adults, scheduled to receive ChAdOx1-nCoV-19 as their second dose of primary COVID-19 vaccination, were enrolled. Participants were classified into two groups based on the first dose vaccine as CoronaVac (heterologous group) or ChAdOx1 nCoV-19 (homologous group). The primary outcome was antibodies to the SARS-CoV-2 spike protein receptor binding domain (anti-RBD) titres at 28 days after the second dose of vaccination. Secondary outcomes were anti-RBD titres at 90 days, surrogate viral neutralizing test (sVNT) at 28 and 90 days, and adverse events.

Findings: In 358 participants with correct vaccine interval, the anti-RBD geometric mean titre ratio for the heterologous versus homologous group was 0.55 (95%CI; 0.44-0.067); p < 0.001 at day 28, and 0.80 (95%CI; 0.65-1.00); P = 0.05 at day 90. Median sVNT neutralizing activity was not significantly different in the heterologous versus homologous group at 28 days (93.5 vs 92.7 %); p = 0.13, but significantly higher in the heterologous group at day 90 (82.9 vs 76.4 %); p = 0.01.

Interpretation: The homologous vaccination resulted in higher anti-RBD titres at 28 days after vaccination, but titres in the homologous group showed more rapid decline at 90 days. In the sVNT assay, median neutralization was similar at 28 days, but was longer-lasting and higher in the heterologous group at 90 days.

Funding: This research received funding from the Royal College of Physicians of Thailand special grant 2021 for research initiative during COVID-19 pandemic.