Two doses of AstraZeneca-Oxford University’s 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 published today in New England Journal of Medicine.
The double-blind multicenter study, led by scientists from the South African Medical Research Council’s Vaccine and Infectious Diseases Analytical Research Unit, studied the safety and efficacy of the AstraZeneca ChAdOx1 nCoV-19 vaccine in HIV-negative adults between 18 and 64 years old who received two standard doses of the vaccine or a placebo in a 1: 1 ratio with a 21 to 35 day interval from June 24 to November 9, 2020. The median follow-up after the second dose was 121 days.
10.4% efficacy against the variant
Of the 750 participants who received the vaccine, 19 (2.5%) developed mild to moderate COVID-19 more than 14 days after the second dose, compared with 23 of the 717 who received placebo (3.2%). The incidence of COVID-19 among the vaccine group was 731 per 1,000 person-years, compared with 93.6 per 1,000 person-years among the placebo group, for an efficacy of 21.9% (confidence interval of 95% [CI], -49.9 to 59.8).
Of the total of 42 cases of COVID-19, 39 (92.9%) were caused by B1351, for a vaccine efficacy against this variant of 10.4% (95% CI, -76.8 to 54, 8). All 42 cases were mild to moderate and no patient was hospitalized.
“In this trial, we found that two doses of the ChAdOx1 nCoV-19 vaccine were not effective against variant B.1.351 in preventing mild to moderate COVID-19,” wrote the authors. “The lack of effectiveness against variant B.1.351 should be considered in the context of the 75% effectiveness (95% CI, 8.7 to 95.5) in preventing mild to moderate COVID-19 starting at least 14 days after a single dose of the ChAdOx1 nCoV-19 vaccine seen before the emergence of variant B.1.351 in South Africa. “
Second generation vaccines under development
Comparison of pseudovirus and live virus neutralization assays against the original D614G and B1351 strain used to test serum from 25 participants 14 days after the booster dose suggested that both were more resistant to B1351 in vaccine samples than in recipient samples. placebo.
Rates of serious adverse events were similar between the vaccine and placebo groups. There was only one serious vaccine-related event, fever of 40 ° C (104 ° F) after the first dose; the fever subsided within 24 hours and no adverse events were observed after the participant’s second dose.
The authors warned that the lack of serious cases of COVID-19 in the study was probably a reflection of the relatively young average age of the participants (30 years) and, therefore, that the trial could not determine whether the AstraZeneca vaccine is effective against serious infections with the B1351 variant.
They said that the degree to which the effectiveness of other COVID-19 vaccines may also be affected by variants with mutations comparable to those of B1351 and P1, the strain first identified in Brazil, may depend on the extent of the neutralizing antibody generated by vaccination.
“If an increased antibody response resulting from 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 variant B.1.351 than that observed in our essay, it is not known “, wrote the researchers.
They concluded by saying that while the development of second-generation COVID-19 vaccines against strains such as B1351 and P1 has begun, the only vaccines that are likely to be available for the rest of 2021 are formulated against the original virus. Until then, the AstraZeneca vaccine is likely to be the most affordable and cheapest coronavirus vaccine.
“Decisions about the usefulness of the ChAdOx1 nCoV-19 vaccine also need to be made in the context of continued global spread and community transmission of variant B.1.351 and the evolution of other SARS-CoV-2 strains that include similar mutations,” said the researchers. authors.
In early February, South African health officials stopped launching the AstraZeneca-Oxford vaccine to investigate reports that it offered little protection against mild to moderate illness. He started using the Johnson & Johnson vaccine to immunize healthcare professionals.