Immunogenicity and safety of AZD1222 (ChAdOx1 nCoV-19) against SARS-CoV-2 in Japan: a double-blind, randomized controlled phase 1/2 trial

Abstract

Background: Immunogenicity and safety of the AZD1222 (ChAdOx1 nCoV-19) vaccine was evaluated in Japanese adults in an ongoing phase 1/2, randomized, double-blind, parallel-group, placebo-controlled, multi-centre trial (NCT04568031).

Methods: Adults (n=256, age ≥18 years) seronegative for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were stratified by age into 18-55- (n=128), 56-69- (n=86) and ≥70-year-old cohorts (n=42), and randomized 3:1 to receive AZD1222 or placebo (two intramuscular injections 4 weeks apart). Immunogenicity and safety were coprimary endpoints. Data collected up to Day 57 are reported.

Results: Positive seroresponses to SARS-CoV-2 spike and receptor-binding domain antigens were seen in all 174 participants who received two doses of AZD1222. Neutralizing antibody seroresponses were seen in 67.5%, 60.3% and 50.0% of participants receiving AZD1222 aged 18-55, 56-69 and ≥70 years, respectively. Solicited adverse events (AEs) were typically mild/moderate in severity and included pain and tenderness at the injection site, malaise, fatigue, muscle pain and headache. Common unsolicited AEs included pain and tenderness at the injection site, fatigue and elevated body temperature. No vaccine-related serious AEs or deaths were reported.

Conclusions: AZD1222 elicited a strong humoral immune response against SARS-CoV-2, and was well tolerated in Japanese participants, including elderly participants.

Keywords: AZD1222; COVID-19; ChAdOx1 nCoV-19; Elderly adult; Humoral response; Japan.

Conflict of interest statement

Conflict of interest statement JV was an employee and stockholder of AstraZeneca at the time of the study. All other authors are employees of, and hold or may hold stock in, AstraZeneca.

Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1

Participant disposition (CONSORT). aIncluding all participants who received at least one dose of study intervention. bHad seroresponse (≥4-fold rise in titre from Day 1 baseline value) to nucleocapsid antibodies by Meso Scale Discovery serology assay up to Day 57. cHad protocol deviations judged to have potential to interfere with the generation or interpretation of an immune response. The study was interrupted temporarily following the occurrence of serious adverse events in clinical trials outside Japan. All screen failures categorized as ‘Sponsor decision’ were associated with this interruption and a consequent pause in enrolment.

Figure 2

Box plots and individual plots of anti-spike antibody titres over time after two doses of AZD1222 or placebo in Japanese participants (fully vaccinated analysis set), determined by Meso Scale Discovery serological assay. The bottom and top edges of the box indicate the first and third quartiles [the difference is the interquartile range (IQR)], the line inside the box is the median, and the diamond mark inside the box is the geometric mean. The whiskers that extend from the box indicate the minimum and maximum within the range of 1.5 × IQR from the box. Box plots are created using log-transformed values. Titre values measured as below the lower limit of quantification (LLoQ) (33) are imputed to a value that is half of the LLoQ. Titre values measured as above the upper limit of quantification (ULoQ) (2,000,000) are imputed at the ULoQ value. AU/mL, arbitrary units per mL; S, SARS-CoV-2 spike antigen.

Figure 3

Box plots and individual plots of anti-receptor-binding domain (RBD) antibody titres over time after two doses of AZD1222 or placebo in Japanese participants (fully vaccinated analysis set), determined by Meso Scale Discovery serological assay. The bottom and top edges of the box indicate the first and third quartiles [the difference is the interquartile range (IQR)], the line inside the box is the median, and the diamond mark inside the box is the geometric mean. The whiskers that extend from the box indicate the minimum and maximum within the range of 1.5 × IQR from the box. Box plots are created using log-transformed values. Titre values measured as below the lower limit of quantification (LLoQ) (204) are imputed to a value that is half of the LLoQ. Titre values measured as above the upper limit of quantification (ULoQ) (2,000,000) are imputed at the ULoQ value. AU/mL, arbitrary units per mL.

Figure 4

Box plots and individual plots of neutralizing antibody (nAb) titres over time after two doses of AZD1222 or placebo in Japanese participants (fully vaccinated analysis set), determined by pseudo-virus neutralization assay. The bottom and top edges of the box indicate the first and third quartiles [the difference is the interquartile range (IQR)], the line inside the box is the median, and the diamond mark inside the box is the geometric mean. The whiskers that extend from the box indicate the minimum and maximum within the range of 1.5 × IQR from the box. Box plots are created using log-transformed values. Titre values measured as below the lower limit of quantification (LLoQ) (40) are imputed to a value that is half of the LLoQ. Titre values measured as above the upper limit of quantification (ULoQ) (787,339) are imputed at the ULoQ value.

Figure 5

Solicited local adverse events in the first 7 days after any dose of AZD1222 or placebo for participants aged (A) 18–55 years, (B) 56–69 years and (C) ≥70 years (total vaccinated analysis set). Day 1 is the day of vaccination. Participants with more than one event within one interval and category are counted once for maximum severity.

Figure 6

Solicited systemic adverse events in the first 7 days after any dose of AZD1222 or placebo for participants aged (A) 18–55 years, (B) 56–69 years and (C) ≥70 years (total vaccinated analysis set). Day 1 is the day of injection. Participants with more than one event within one interval and category are counted once for maximum severity.