A paper published in the New England Journal of Medicine (NEJM) looks at results from the phase 2a-b trial of Novavax COVID-19 vaccine in South Africa.
Dr Peter English, Retired Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice Magazine, Immediate past Chair of the BMA Public Health Medicine Committee, said:
“In the UK we are most familiar with two types of Covid-19 vaccine: mRNA, and adenovirus vector vaccines. The Novavax vaccine is in some ways a more traditional type of vaccine. Instead of smuggling the genetic material for the antigen into cells, so that our own cells produce the antigen, Novavax comprises the antigen itself in the form of “nanoparticles”.
“We have seen data on this vaccine published in press releases1. I have been unable to find a paper in peer-reviewed describing a phase III or post-implementation study of this vaccine, although at least one phase I/II preprint is available2. This paper is a further “phase 2a-b” trial.
“This study was undertaken in South Africa, at a time when most infections were caused by the B.1.351 variant.
“Phase I and II trials are smaller than phase III trials. Their function is to test for safety, and to give a broad estimate of how effective the vaccine might be. They may also use different doses and prime-boost intervals, in order to estimate the optimum regime.
“In this randomised controlled trial (RCT) there were initially 6324 participants – large for a phase II trial, but smaller than the ≥10,000 numbers usually used for a phase III trial. Approximately 30% of the participants were already seropositive for SARS-CoV-2, indicating that they had already developed an immune response to the virus, presumably due to natural infection. After exclusions, cases lost to follow-up and so on, there were 1357 participants in the vaccine group, and 1327 in the placebo group.
“Among these 2684 who were not already seropositive, 15 in the group who received two doses of the vaccine developed confirmed, symptomatic Covid-19 infection at least 7 days after the second dose; compared to 29 in the group given two doses of placebo. This worked out as 49.4% vaccine efficacy. The cases were “predominantly mild-to-moderate Covid-19”.
“About 1 in 20 of the participants (6%) was HIV-positive; and if these are excluded, the vaccine efficacy was marginally better at 51%, with efficacy in those who were HIV-negative being 60.1%.
“In 41 of the 44 (15+29) cases, the virus was sequenced, and most – 38/49 (92.7%) were the B.1.351 variant.
“With only 44 cases, the confidence intervals will inevitably be large.
“The average age of the participants was quite young – 32 years. This might explain the relatively low rates of more serious forms of Covid-19, and the trial’s consequent inability to distinguish between efficacy against different severities of disease.
“The safety of the vaccine was study was done in part to study vaccine safety; and in this respect it was reassuring.
“The analysis seems to have been done well and, subject to the relatively small numbers, the data are robust.
“It is very hard to compare this study with others. The vaccine is a different type of vaccine; and the study was undertaken in a population where the predominant variant was the B.1.351 variant. There have been some indications that, in vitro at least (studies of neutralising antibody titres) vaccines may be less effective against this variant; so we cannot compare the relatively low efficacy of this vaccine with studies of other vaccinations in which this variant was not widespread.
“The fact that so few participants developed more severe forms of Covid-19 makes it impossible from this trial to know if the vaccine is more effective at preventing more severe disease; and this is one of the most important factors in determining the usefulness of a vaccine. Most vaccines are less effective at preventing mild disease than they are at preventing severe disease; so this vaccine could turn out to be much more effective at preventing hospital admissions and deaths – we simply don’t know, yet.
“It would certainly be valuable to have a vaccine made using different technologies in our armamentarium, in case problems (such as immunity to vectors impairing future effectiveness) arise.
“We accept vaccine effectiveness rates of around about 51% for influenza vaccines (which vary considerably in their effectiveness from year to year, partly dependent on the quality of the match with circulating virus strains); halving the number of cases is very valuable. On the other hand, if the real-world effectiveness, or the efficacy in large phase III trials is considerably lower than for other vaccines (taking into consideration factors such as the prevalence of variants such as the B.1.351 variant, and of HIV), it would argue in favour of using more effective vaccines. However, I must stress again, that we do not yet have data that permits a comparison of vaccines in this way.”
1 Novavax. Novavax COVID-19 Vaccine Demonstrates 89.3% Efficacy in UK Phase 3 Trial. Press release 2021; https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3. Accessed 13 Apr, 2021.
2 Keech C, Albert G, Reed P, et al. First-in-Human Trial of a SARS CoV 2 Recombinant Spike Protein Nanoparticle Vaccine. medRxiv. 2020:2020.2008.2005.20168435. https://doi.org/10.1101/2020.08.05.20168435
‘Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant’ by V. Shinde et al. was published in the NEJM at 22:00 UK time on Wednesday 5 May 2021.
Dr Peter English: “No conflicts of interest to declare.”