ChAdOx1 nCoV-19, a replication-defective chimpanzee adenovirus-vectored vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appears to be safe and immunogenic in older adults, according to study results published in the Lancet.
This single-blind, randomized, phase 2 component of a phase 2/3 trial (ClinicalTrials.gov identifier: NCT04400838) conducted at 2 sites in the United Kingdom compared the safety, reactogenicity, and immunogenicity of ChAdOx1 nCoV-19 (AstraZeneca, Cambridge, United Kingdom) with the quadrivalent MenACWY protein-polysaccharide conjugate vaccine as a comparator in 560 participants in 3 age groups (18-55 years, 56-69 years, and ≥70 years). Older adults were enrolled only after ChAdOx1 nCoV-19 was deemed safe in adults aged 18 to 55 years. ChAdOx1 nCoV-19 was administered as a single-dose or 2-dose regimen (28 days apart) at either a low dose or standard dose. Investigators randomly assigned participants to 1 of 10 different groups.
Adults aged 18-55 years were randomly assigned in a 1:1 ratio in the low-dose cohort (n=100) and 5:1 ratio in the standard-dose cohort (n=60) to receive 2 doses of either ChAdOx1 nCoV-19 or MenACWY. Adults aged 56-69 years (3:1:3:1) and aged 70 years or older (5:1:5:1) were randomly assigned to receive 1 dose of ChAdOx1 nCoV-19, 1 dose of MenACWY, 2 doses of ChAdOx1 nCoV-19, or 2 doses of MenACWY.
Humoral responses were assessed at baseline and after each vaccination until 1 year after the booster using assays of anti-spike protein immunoglobulin (Ig)G and neutralizing antibody titers. Primary outcomes were to assess efficacy, measured by number of symptomatic, virologically confirmed COVID-19 cases, and safety, measured by occurrence of serious adverse events. Secondary outcomes were safety, reactogenicity, immunogenicity profiles in patients greater than 56 years of age, efficacy against severe and non-severe COVID-19, death, and seroconversion against non-spike proteins.
Of the 560 participants enrolled, 552 completed the study. Overall, 50% of participants were women, 95% were White, and 98% were non-smokers. The median age was 43.0 years in the 18 to 55 years group, 60.0 years in the 56 to 69 years group, and 73.0 years in the 70 years and older group.
Local and systemic reactions were more common with ChAdOx1 nCoV-19 than with MenACWY with the standard dose, but reactions decreased with increasing age. At least 1 local symptom was reported in 88% (43/49), 73% (22/30), and 61% (30/49) of participants in the 18 to 55 years, 56 to 69 years, and 70 years and older groups, respectively. The proportion of local symptoms reported was similar after the boost vaccination. The most commonly solicited systemic adverse reactions were fatigue, headache, feverishness, and myalgia. There was a similar pattern in all the age groups with the low-dose ChAdOx1 nCoV-19 after the prime and booster vaccination.
There were 13 serious adverse events during the study period, but none were considered to be vaccine-related.
Anti-spike IgG responses at day 28 decreased with increasing age for both dose levels and for all dose groups. By day 28 after the boost vaccination, similar antibody titers were seen across all 2-dose regimen groups, regardless of age or vaccine dose. In the standard dose groups, median titer values were 20,713 AU/mL for patients aged 18-55 years (n=39), 16,170 AU/mL for patients aged 56-69 years (n=26), and 17,561 for patients aged 70 and older (n=47); P =.68.
No significant differences were seen in neutralization titers between low-dose and standard-dose vaccine recipients at the same time point within each age group (18–55 years, P =.33; 56–69 years, P =.12; ≥70 years, P =.62). More than 99% of participants in the boost dose groups had neutralizing antibodies 14 days after the boost vaccination.
Spike-specific T-cell responses peaked at 14 days after the prime vaccination and did not increase significantly after the boost vaccination (P =.46).
Aside from the single-blind design, the study’s limitations included a small sample size for participants older than 80 years, and few participants with chronic illness or frailty. Larger studies are underway to assess the efficacy of ChAdOx1 nCoV-19 in all age groups and older adults with a wide range of comorbidities.
Disclosure: Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Ramasamy MN, Minassian AM, Ewer KJ, et al; Oxford COVID Vaccine Trial Group. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Lancet. Published online November 18, 2020. doi:10.1016/S0140-6736(20)32466-1