Two doses of the AstraZeneca-Oxford University COVID-19 vaccine were ineffective against mild to moderate infections with the B1351 variant first identified in South Africa, according to a phase 1b-2 clinical trial conducted today in the New England Journal of Medicine.
The double-blind multi-center study, led by scientists from the South African Medical Research Council, for the Vaccine and Infectious Diseases Research Unit, studied the safety and efficacy of the AstraZeneca ChAdOx1 nCoV-19 vaccine in HIV-negative adults aged up to 64 years. either two standard doses of the vaccine or a placebo in a 1: 1 ratio of 21 to 35 days, from 24 June to 9 November 2020. The median follow-up after the second dose was 121 days.
10.4% efficiency versus variant
Of the 750 participants who received vaccine, 19 (2.5%) developed mild to moderate COVID-19 more than 14 days after the second dose, compared with 23 of 717 placebo recipients (3.2%). The incidence of COVID-19 among the vaccine group was 731 per 1,000 person-years, compared to 93.6 per 1,000 person-years among the placebo group, for an efficacy of 21.9% (95% confidence interval [CI], -49.9 to 59.8).
Of the 42 total cases of COVID-19, 39 (92.9%) were caused by B1351 for a vaccine efficacy at this variant of 10.4% (95% GI, -76.8 to 54.8). All 42 cases were moderate to moderate, and no patients were admitted to the hospital.
“In this experiment, we found that two doses of the ChAdOx1 nCoV-19 vaccine had no efficacy over the B.1.351 variant to prevent COVID-19 from moderate to moderate,” the authors wrote. “The lack of efficacy against the B.1.351 variant should be considered in the context of the 75% efficacy (95% AI, 8.7 to 95.5) of COVID-19 with a mild to moderate appearance occurs with at least 14 days after even a single dose of ChAdOx1 nCoV-19 vaccine observed before the B.1.351 variant originated in South Africa. “
Second-generation vaccines in development
Comparison of pseudovirus and live virus neutralization assays with the original D614G strain and B1351 used to test 25 participants’ serum 14 days after the booster dose suggested that both were more resistant to B1351 in vaccinated samples than in placebo samples. -recipients.
Serious side effects were similar between the vaccine and placebo groups. Only one serious vaccine-related event occurred, a fever of 40 ° C (104 ° F) after the first dose; the fever was eliminated within 24 hours, and no adverse events were seen after the second dose of the participant.
The authors warned that the lack of severe COVID-19 cases in the study was likely to reflect the relatively young average age of participants (30 years) and that the trial could therefore not determine whether the AstraZeneca vaccine was effective against severe infection with the B1351 variant.
They said the extent to which the efficacy of other COVID-19 vaccines may also be affected by variants with mutations similar to those of B1351 and P1, the strain first identified in Brazil, depends on the extent of neutralizing antibody generated by vaccination.
“Whether an enhanced antibody response due to a longer interval between the first and second doses of the ChAdOx1 nCoV-19 vaccine, as described elsewhere, may confer better residual neutralizing antibody activity against the B.1.351 variant than in our experiment observed is not known, ‘the researchers wrote.
They concluded by saying that although the development of second-generation COVID-19 vaccines against strains such as B1351 and P1 had begun, the only vaccines likely to be available for the rest of 2021 were formulated against the original virus. Until then, the AstraZeneca vaccine will probably be the most accessible and cheapest vaccine against coronavirus.
“Discussions on the utility of the ChAdOx1 nCoV-19 vaccine should also be conducted in the context of ongoing worldwide distribution and community transmission of the B.1.351 variant and the evolution of other SARS-CoV-2 strains that include similar mutations, “said the authors.
In early February, South African health officials halted the explosion of the AstraZeneca-Oxford vaccine to investigate reports that it offers little protection against mild to moderate illness. This led to the use of the Johnson & Johnson vaccine to immunize health workers.