EXPERT REACTION: How COVID vaccines are handling the new variants

There is concern about the ability of current vaccines to confer immunity against the new variants of the SARS-CoV-2 virus currently circulating. Two new studies have been published recently which address this issue.

Study 1:

A recent study published in Nature Medicine suggests the Pfizer-BioNTech COVID-19 vaccine (BNT162b2) is shown to neutralise SARS-CoV-2 with the N501Y and E484K mutations.

This was a small in-vitro [in the test tube] study in which a panel of sera from 20 participants who had previously been immunised with the Pfizer-BioNTech vaccine was tested in the laboratory for activity against the non-mutant strain of the virus as well as engineered mutant viruses. The authors reported that the vaccine was 81 per cent as effective at neutralising engineered virus. Specifically, they found that neutralisation against the E484K mutation - a mutation unique to the South African variant - was slightly lower than neutralisation against the N501Y mutation, which is shared by both the South African and the United Kingdom variants.

Whilst positive, these findings need to be interpreted with some caution. They are preliminary findings from only 20 participants. Also, they provide only indirect evidence for the effectiveness of the vaccine against the new strains, as these were laboratory studies using engineered virus and they only looked at one aspect of the immune response, the antibody response. These studies did not address the effect of these mutations on cell-mediated immunity, which is likely to also play an important role in the immune response primed by the vaccine.

Study 2:

A study showing that the AstraZeneca vaccine may only have an efficacy of 10 per cent against the South African variant.

This study suggests that the Oxford/AstraZeneca vaccine may only have an efficacy of 10 per cent against mild to moderate infection. Whilst this is not good news, this finding needs to be put in perspective. This was a small-scale trial of 2,000 young people. What it suggest is that individuals may still get ill after receiving the vaccine if exposed to the South African variant of the virus. It is hoped that the vaccine is still going to protect against severe infection, hospitalisation and death, though this could not be ascertained from this study as it focussed on young people who do not generally get severe illness.

More work needs to be completed to understand the effect of vaccines against the new variants of the virus. We are fortunate, however, that the vaccine platforms being used allow for vaccine design to be updated to combat new strains as they emerge.

The data reported from South Africa for the AstraZeneca vaccine are very concerning, and were enough to cause the government there to pause the planned rollout of the vaccine. Whilst there is uncertainty about the 10 per cent efficacy against the B1351 variant, it is unlikely to fluctuate substantially from that value with further data. This compares to over 60 per cent efficacy reported for Novavax against the same South African mutant. Whilst we have not seen efficacy estimates for Pfizer, the research published in Nature Medicine shows pretty reasonable virus neutralisation against the South African variant. This suggests there will be reasonable efficacy against the South African strain.

Even for the primary endpoint of symptomatic infection with the G614 variant which was dominant in 2020, the Pfizer [vaccine] is far superior to the AstraZeneca vaccine, so it is not surprising that for other outcomes (like protection against variants of concern) that there is a difference between the vaccines.  

The Johnson and Johnson vaccine also reports better efficacy (57 per cent) against moderate or severe disease with the South African strain.  We also know the Moderna vaccine has no negative impact on neutralising titres against the B.1.1.7, and a six-fold reduction in neutralizing titres against the B.1.351, but neutralising titre levels with B.1.351 above levels that are expected to be protective. The mRNA vaccines seem to be the best, with Novavax also very good (although the phase 3 trials are not yet published).

The mutations emerging in the UK, Brazil and South Africa are likely to become the dominant strains globally in 2021, just like the fitter G614 variant which took over from the original Wuhan strain in 2020.  

We know most of the breaches in hotel quarantine, which is the likely source of any outbreak in Australia, have been due to these variants of concern. Therefore, we need to be able to pivot rapidly to a changing viral landscape.  

A pandemic is not a static scenario - things can change rapidly, and if one of these variants of concern caused an epidemic in Australia, we need to have the most effective vaccines against them. In the medium term, all vaccine manufacturers can adjust their vaccines to match emergent mutants, and I expect AstraZeneca will do so. But for now, the AstraZeneca vaccine may not be enough. We should be looking at options with the other two vaccines in our portfolio, Pfizer and Novavax.

It has been fascinating to follow the evolution of this virus so closely given the high rates of sequencing in so many countries. With a virus as prevalent as this, mutations are inevitable, however, to have them detected and reported essentially in real-time has us in a good position to be able to respond. But these reports do need to be considered in context.

When we do see new strains or variants emerge with significant changes it is important to understand how these changes impact not only the phenotype and therefore epidemiology of the virus but also how the efficacy of vaccines (and potentially therapies) are impacted. We are now hearing many such reports from the leading vaccine candidates. However, thus far the majority have been relatively small studies, yet to be peer-reviewed, and not really set up in a controlled way to truly allow head-to-head comparison of efficacy rates.

There are also many laboratory studies that provide very useful information, but this does not always translate perfectly to tell us what is likely to happen in the real world. The report overnight from Nature Medicine that the Pfizer-BioNTech vaccine still neutralises SARS-CoV-2 with the N501Y and E484K mutations in a study of sera from 20 vaccine recipients is certainly promising, but I agree with the conclusion of this study that ongoing monitoring is required.

The recently reported study that suggested the Oxford/AstraZeneca vaccine candidate offered significantly reduced protection against the South African variant similarly needs to be considered in context. This was a small study in a narrow age range that showed reduced protection against mild to moderate cases.

It is thought plausible that this vaccine could still have a meaningful impact on preventing hospitalisations and death from this strain, which is obviously still very important, and recent data suggests that with the standard dose and a longer dosing interval, the efficacy of this vaccine is likely higher than previously reported at 82.4 per cent. In addition, the Oxford/AstraZeneca team is working on additional candidates to address these new variants should they be required.

My opinion, therefore, is that it is too early to change our position with respect to any of the vaccine candidates likely to be utilised in this country, but we do need to carefully monitor the situation and all available evidence moving forward.