One of the variants of the SARS-CoV-2 virus may impact the effectiveness of the AstraZeneca COVID-19 vaccine (ChAdOx1). In this case, the so-called South African variant, B.1.351, has shown to significantly reduce the efficacy of the vaccine. This has become a worrisome issue as the world tries to move away from this pandemic.
Of course, there are only a handful of new COVID-19 strains that are actually dangerous, but the issues are whether the new vaccines from Pfizer, Moderna, JNJ, and AstraZeneca confer immunity to any new variants and what regulatory requires may be necessary for the vaccine manufacturers to respond to them.
It’s important for us to keep abreast of these variants and speculate on how we might move forward to protect people. That’s why we need to understand how this new SARS-CoV-2 variant impacted the effectiveness of the AstraZeneca-Oxford COVID-19 vaccine.
About the new COVID-19 virus strains
There are five main SARS-CoV-2 “Variants of Concern” according to the CDC as of 18 March 2021:
- B.1.1.7 – In the United Kingdom (UK), a variant of SARS-CoV-2 known as B.1.1.7 emerged. This variant carries a large number of mutations and has since been detected around the world, including in the United States (US). This variant was first detected in the US at the end of December 2020. In January 2021, scientists from the UK reported early evidence that suggests the B.1.1.7 variant may be associated with an increased risk of death compared with other variants. More studies are needed to confirm this finding.
- B.1.351 – In South Africa, another strain of SARS-CoV-2 known as B.1.351 emerged independently of B.1.1.7. According to a non-peer-reviewed preprint article, this variant shares some mutations with B.1.1.7. Cases attributed to B.1.351 have been detected outside of South Africa, and this variant was first detected in the US at the end of January 2021. Preliminary evidence from non-peer-reviewed publications suggests that the Moderna COVID-19 mRNA vaccine currently used in the US may be less effective against this new strain.
- P.1 – In Brazil, a variant of SARS-CoV-2 known as P.1 was first identified in January 2021 in travelers from Brazil who arrived in Japan. This variant was detected in the US at the end of January 2021. There is evidence to suggest that some of the mutations in the P.1 variant may affect the ability of antibodies (from natural infection or vaccination) to recognize and neutralize the virus.
- B.1.427 – This is the first of two variants that have been discovered in California. This variant shows a 20% increased transmissibility, according to a pre-print article. The virus shows a moderate reduction in neutralizing antibodies, post-vaccination.
- B.1.429 – This California variant is very similar to the B.1.427 variant.
Mutations in viruses occur naturally over time whenever an animal or human is infected by that virus. Some viruses, such as influenza, have a fairly high rate of mutation, while others do not.
While the SARS-CoV-2 virus spreads, a certain level of genetic mutations occurs over time. Many mutations have no effect on the infectivity or the danger from the virus. Most mutations are deleterious, and that strain may die out. However, some mutations, like the ones listed above, cause these new COVID-19 strains to outcompete others because the mutations are more beneficial to the virus.
Here’s the important point – mutations only occur if the virus replicates. So even if a vaccine, such as the AstraZeneca COVID-19 vaccine, has reduced effectiveness against some strains, it still slows the spread of the disease which reduces the risk of variants that can spread quickly.
In addition, the mutation rate for coronaviruses is significantly lower than influenza viruses, which recombine frequently into different strains that are unknown to the immune system, despite vaccination or prior infection. That’s why the flu keeps coming back every season.
Variants and COVID-19 vaccines
The CDC and other public health agencies closely monitor these new COVID-19 variants because they might be dangerous and reduce vaccine effectiveness. Thus, they attempt to determine the following as quickly as possible:
- The ability of the new COVID-19 strain to spread more quickly in people.
- The ability of the new strain to cause either milder or more severe disease in people.
- The ability to evade detection by specific diagnostic tests.
- Decreased susceptibility to therapeutics that employ monoclonal antibodies. Monoclonal antibody therapy requires specifically designed antibodies that target unique regions of the virus to block its replication or infection. If a new mutation causes the virus to avoid the antibody, then the therapy may be less effective.
- Ability to evade natural or vaccine-induced immunity. This may be quite rare because the typical immune response, which employs polyclonal antibodies, targets various parts of the antigenic portions of the virus. It would take several mutations to reduce the natural or vaccine-induced immunity, but it’s important to monitor these mutations in case the new COVID-19 strains begin avoiding the immune response.
AstraZeneca COVID-19 vaccine effectiveness
Right now, we don’t have large clinical trials to determine the vaccine effectiveness against the new COVID-19 strains for the four currently (or nearly currently) available vaccines from Pfizer, Moderna, AstraZeneca, and JNJ (Johnson and Johnson).
A new article in the New England Journal of Medicine examines the effectiveness of the AstraZeneca COVID-19 vaccine against the B.1.351 variant that first arose in South Africa. And the results are not encouraging, at least for this vaccine.
The clinical trial enrolled 2026 HIV-negative adults (average age, 30 years) between 24 June and 9 November 2020. Of those, 1010 received the placebo, and 1011 received at least one dose of the AstraZeneca vaccine. Five dropped out of the trial.
- The study found that about 3.2% of placebo recipients compared to 2.5% of vaccine recipients developed mild-to-moderate COVID-19. This is equivalent to a vaccine effectiveness of 21.9%.
- Among the 42 individuals who developed COVID-19, 39 was caused by the B.1.351 variant. Against this variant, the vaccine effectiveness was 10.4%.
The authors concluded:
A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant.
This is not good news about the effectiveness of the AstraZeneca COVID-19 vaccine, especially against the B.1.351 variant.
However, I think a couple of caveats need to be pointed out. First, this is an extremely small sample size – out of a total of 2026 participants, only 42 contracted the disease. This is why the clinical trials for these vaccines have been very large. Second, because the sample size is so small, the margin of error is rather large.
So what does this say about other COVID-19 vaccines? It’s hard to say.
As I wrote above, these vaccines induce polyclonal antibodies so the immune system could recognize several different parts of the S-protein, the spike that causes the SARS-CoV-2 virus to attach to cells. Thus, it would take a lot of mutations to that spike before vaccines become totally ineffective.
Although these variants may not be too concerning, the B.1.351 variant from South Africa may not be as neutralized as well by antibodies elicited by the other vaccines. We actually only have data on the AstraZeneca vaccine, we don’t have anything as of yet from the JNJ, Pfizer, and Moderna COVID-19 vaccines.
Without a ton of evidence (or any good evidence at all), it appears that the mRNA vaccines from Pfizer and Moderna perform better against the new COVID-19 strains compared to the adenovirus-based vaccines from JNJ and AstraZeneca. But there are so many differences between the two classes of vaccines, it’s hard to tell.
However, the good thing about the mRNA vaccines is that they can be easily reformulated to deal with new SARS-CoV-2 variants. The sequence for a newly mutated S-protein on the virus can be isolated to create a new mRNA fragment for a revised vaccine. This can be done very quickly.
Summary
The FDA has decided that they will permit immunogenicity data, booster studies to support “strain changes” to an authorized COVID-19 vaccine rather than requiring new, large clinical trials. This decision will allow amendments to the Emergency Use Authorizations for the vaccines.
To forestall anti-vaccine activist gripes about this, this change doesn’t mean that the FDA will overlook any safety or effectiveness issues. As long as there are no other changes to the vaccine except for the “strain change,” the evidence supporting its safety doesn’t change.
This is similar to the flu vaccine, where a full clinical trial isn’t required as long as the only change to the vaccine is the antigen. Because COVID-19 is so deadly, it is important that we respond to new COVID-19 strains as quickly as possible to prevent a new pandemic or surge.
However, irrespective of the current vaccine’s effectiveness against these various strains, the transmission of SARS-CoV-2 between humans is what causes new mutations, because more infective and potentially deadly variants are selected for. Vaccinating a large proportion of the population against the disease, causes the mutation rate to decrease. And with fewer variants, the vaccines work better. It’s a positive feedback loop.
I think that if you speak to experts on this disease they are confident in the vaccine’s ability to fight against the new mutations, but I’m sure they lose sleep at night that new variant arises that avoids the immune responses of those who were vaccinated or contracted the disease. I lose sleep because of that concern.
But for the time being, I think the evidence probably supports the effectiveness of the four vaccines against the diseases. However, because we can’t be sure, that means public health initiatives, like facemasks and social distancing, still need to be followed. But the pharmaceutical companies behind the vaccines are preparing for “just in case.”
Notes
I need to clarify the terminology I use in this article. COVID-19 is a disease caused by the SARS-CoV-2 virus. Technically, COVID-19 does not mutate, just the virus.
In addition, mutations, strains, and variants are somewhat interchangeable terms that describe different viruses. However, the mutation is a technical change in the DNA, while variants and strains can be considered subspecies (or sub-subspecies) of the coronavirus. So, calling it a COVID-19 variant or strain is accurate, it is technically not how we should describe it.
Citations
- Madhi SA, Baillie V, Cutland CL, Voysey M, Koen AL, Fairlie L, Padayachee SD, Dheda K, Barnabas SL, Bhorat QE, Briner C, Kwatra G, Ahmed K, Aley P, Bhikha S, Bhiman JN, Bhorat AE, du Plessis J, Esmail A, Groenewald M, Horne E, Hwa SH, Jose A, Lambe T, Laubscher M, Malahleha M, Masenya M, Masilela M, McKenzie S, Molapo K, Moultrie A, Oelofse S, Patel F, Pillay S, Rhead S, Rodel H, Rossouw L, Taoushanis C, Tegally H, Thombrayil A, van Eck S, Wibmer CK, Durham NM, Kelly EJ, Villafana TL, Gilbert S, Pollard AJ, de Oliveira T, Moore PL, Sigal A, Izu A; NGS-SA Group Wits–VIDA COVID Group. Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant. N Engl J Med. 2021 Mar 16. doi: 10.1056/NEJMoa2102214. Epub ahead of print. PMID: 33725432.
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