A randomized clinical trial of a booster dose with low versus standard dose of AZD1222 in adult after 2 doses of inactivated vaccines

Sira Nanthapisal; Thanyawee Puthanakit; Peera Jaru-Ampornpan; Rapisa Nantanee; Pimpayao Sodsai; Orawan Himananto; Jiratchaya Sophonphan; Pintip Suchartlikitwong; Narin Hiransuthikul; Pornpimon Angkasekwinai; Auchara Tangsathapornpong; Nattiya Hirankarn; study team

doi:10.1016/j.vaccine.2022.03.036

A randomized clinical trial of a booster dose with low versus standard dose of AZD1222 in adult after 2 doses of inactivated vaccines

Vaccine. 2022 Apr 20;40(18):2551-2560. doi: 10.1016/j.vaccine.2022.03.036. Epub 2022 Mar 24.

Affiliations

¹ Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand; Research Unit in Infectious and Immunology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand; Clinical Research Center, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.
² Center of Excellence in Pediatric Infectious Diseases and Vaccines, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Electronic address: thanyawee.p@chula.ac.th.
³ Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC).
⁴ Center of Excellence in Pediatric Infectious Diseases and Vaccines, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Pediatric Allergy and Clinical Immunology Research Unit, Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁵ Center of Excellence in Immunology and Immune-mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁶ Monoclonal Antibody Production and Application Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC).
⁷ The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
⁸ Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁹ Department of Preventive and Social Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
¹⁰ Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, Thailand; Research Unit in Molecular Pathogenesis and Immunology of Infectious Diseases, Thammasat University, Pathumthani, Thailand; Research Unit in Infectious and Immunology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.
¹¹ Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand; Research Unit in Infectious and Immunology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.

Abstract

Background: Immunogenicity of inactivated SARS-CoV-2 vaccine has waning antibody over time. With the emergence of the SARS-CoV-2 delta variant, which requires higher neutralizing antibody to prevent infection, a booster dose is needed.

Objective: To evaluate immunogenicity and reactogenicity of standard- versus low-dose ChAdOx1 nCoV-19 vaccine booster after CoronaVac in healthy adults.

Methods: A double-blinded, randomized, controlled trial of adult, aged 18-59 years, with completion of 2-dose CoronaVac at 21-28 days apart for more than 2 months was conducted. Participants were randomized to receive AZD1222 (Oxford/AstraZeneca) intramuscularly; standard dose (SD, 5x10¹⁰ viral particles) or low dose (LD, 2.5x10¹⁰ viral particles). Surrogate virus neutralization test (sVNT) against wild type and delta variant, and anti-spike-receptor-binding-domain IgG (anti-S-RBD IgG) were compared as geometric mean ratio (GMR) at day 14 and 90 between LD and SD arms.

Results: From July-August 2021, 422 adults with median age of 44 (IQR 36-51) years were enrolled. The median interval from CoronaVac to AZD1222 booster was 77 (IQR 64-95) days. At baseline, geometric means (GMs) of sVNT against delta variant and anti-S-RBD IgG were 18.1%inhibition (95% CI 16.4-20.0) and 111.5 (105.1-118.3) BAU/ml. GMs of sVNT against delta variant and anti-S-RBD IgG in SD were 95.6%inhibition (95% CI 94.3-97.0) and 1975.1 (1841.7-2118.2) BAU/ml at day 14, and 89.4%inhibition (86.4-92.4) and 938.6 (859.9-1024.4) BAU/ml at day 90, respectively. GMRs of sVNT against delta variant and anti-S-RBD IgG in LD compared to SD were 1.00 (95% CI 0.98-1.02) and 0.84 (0.76-0.93) at day 14, and 0.98 (0.94-1.03) and 0.89 (0.79-1.00) at day 90, respectively. LD recipients had significantly lower rate of fever (6.8% vs 25.0%) and myalgia (51.9% vs 70.7%) compared to SD.

Conclusion: Half-dose AZD1222 booster after 2-dose inactivated SARS-CoV-2 vaccination had non-inferior immunogenicity, yet lower systemic reactogenicity. Fractional low-dose AZD1222 booster should be considered especially in resource-constrained settings.

Keywords: AZD1222; Booster dose; ChAdOx1 nCoV-19 vaccine; CoronaVac vaccine; Neutralizing antibody titer; SARS-CoV-2 vaccine; anti-SARS-CoV-2 IgG.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies, Viral
COVID-19 Vaccines* / adverse effects
COVID-19* / prevention & control
ChAdOx1 nCoV-19
Humans
Immunogenicity, Vaccine
Immunoglobulin G
Middle Aged
SARS-CoV-2
Vaccines, Inactivated / adverse effects

Substances

Antibodies, Viral
COVID-19 Vaccines
Immunoglobulin G
Vaccines, Inactivated
ChAdOx1 nCoV-19

Supplementary concepts

SARS-CoV-2 variants