Coronavirus (38) South Africa variant of SARS-CoV-2
In the last blog post, we’ve seen that the B.1.351 variant from South Africa is resistant to the antibodies in convalescent blood from most of the patients who have recovered from COVID-19, and it is also highly resistant to one of the currently-approved monoclonal antibody therapies to COVID-19. This blog post presents you with data on the efficacy of the vaccines that have been granted emergency use for COVID-19 in the UK, against the variant B.1.351.
B.1.351 is highly resistant to mRNA vaccines: Moderna mRNA-1273 and Pfizer BNT162b2
In order to check the efficacy of the mRNA vaccines to different variants, including variant B.1.351 and the original strain of SARS-CoV-2, researchers from Columbia University took blood samples from the volunteers who had received a complete course of either one of the two mRNA vaccines in the initial phase of clinical trials, mRNA-1273 from Moderna (12 participants) and Pfizer BNT162b2 (10 participants), and then performed neutralization tests* against the variants. The blood samples were collected at least 7 days after the last dose of vaccination in order to obtain serum with as high level of immunity as possible.1
They found that, when compared to the original strain, the overall neutralizing activity from the blood samples taken from the participants vaccinated with Moderna mRNA-1273 or with Pfizer BNT162b2, is significantly lower against the B.1.351 variant.1 According to this study, the overall neutralizing activity against B.1.351 was 12.4-fold lower than the original strain using blood samples from people vaccinated with Moderna mRNA-1273, and 10.3 fold lower using blood samples from people vaccinated with Pfizer BNT162b2.1
These results reflect the fact that while both the mRNA vaccines are highly protective against the original strain, they confer much weaker protection from infection by the B.1.351 variant. The people vaccinated with full course of either Moderna mRNA-1273 or Pfizer BNT162b2 still have a very high chance of being infected and getting sick even when high immunity from the vaccines is attained.
When the serum from vaccinated individuals was used to test against pseudoviruses with spike genes containing different mutations found in B.1.351, the researchers found that the E484K mutation confers the resistance to neutralization.1
AZD1222 has low efficacy towards B.1.351
A joint clinical trial study with scientists from the UK and South Africa showed that the efficacy of the two-dose regimen of adenovirus vaccine AZD1222 from AstraZeneca against B.1.351 was only 10.4%,2 whereas the efficacy of AZD1222 against the initial strain of SARS-CoV-2 can be as high as 90%.3
The study was conducted in South Africa between late June and early November last year, when the variant B.1.351 was emerging. It was a multi-centre, double-blind, randomized, controlled trial to assess the safety and efficacy of AZD1222 in people not infected with the human immunodeficiency virus (HIV). Adult participants below the age of 65 were assigned to receive two doses of vaccine or placebo 21 to 35 days apart.2 In the primary end-point analysis, 23 of 717 placebo recipients (3.2%) vs 19 of 750 vaccine recipients (2.5%) developed mild-to-moderate COVID-19, resulting in an efficacy of 21.9% from AZD1222.2
The efficacy result of AZD1222 from the clinical study in South Africa was very different from the previous report.3 However, sequencing analysis of the samples from the 42 participants with COVID-19 provided an explanation. It was found that 39 of the cases were caused by the B.1.351 variant. This led to the finding that vaccine efficacy against B.1.351 was only 10.4%. The study also found that incidence of serious adverse events was nearly equal between the vaccine and placebo groups.2
From this study, it was found that the adenovirus vaccine AZD1222 cannot very much protect vaccinated people against mild-to-moderate COVID-19 due to the B.1.351 variant.2
Conclusion
The B.1.351 South African strain emerged last August and has spread globally since then. Reports showed that the variant will not cause more serious illnesses and is not more deadly than the initial SARS-CoV-2 strain that causes COVID-19. Those people, such as the elderly and the ones with underlying health conditions, who are at high risk under the initial strain are at a similar risk level under the B.1.351 strain.
Although the South Africa variant B.1.351 has 50% higher transmissibility than the initial strain, we may not need to be too worried about the threat from this variant yet. B.1.1.7, one of the dominant strains in the UK, is also 50% higher in transmissibility than the initial strain, yet the COVID-19 infection rate and death toll in the UK is much lower than before. This means that variant strains even with higher transmissibility than the original strain can be contained, although it is not yet known for certain to what extent this containment was due to lockdowns (which will also apply to B.1.351) versus vaccines (which will not).
However, the concern is that the current therapies and vaccines designed against the original virus strain that cause COVID-19 will not work as well against the B.1.351 variant, as shown from the research studies presented in these two blog posts. Moreover, experience from clinical studies of COVID-19 vaccines in South Africa undertaken by Novavax, Janssen and Oxford/AstraZeneca also suggest that the variant B.1.351 can still cause infection even on the people who had been infected with the original strain of SARS-CoV-2. This shows that the immunity conferred from the previous infection by the original strain seems not strong enough to provide protection for the subsequent infection from the variant B.1.351.2,4,5
Therefore, until the B.1.351 variant is totally contained in the UK and/or an effective therapy or vaccine is available, we should stay cautious while the UK government is easing the lockdown restrictions.
*Neutralization is a process where the vaccine/monoclonal antibody acted against a pathogen, such as virus. A pathogen can be highly neutralized by vaccine/monoclonal antibody, which means its activity can be diminished or abolished by the vaccine/monoclonal antibody, i.e. the vaccine or monoclonal antibody is effective against the pathogen.
**Pseudovirus used in the experiments on SARS-CoV-2 refers to a retrovirus that is genetically engineered to carry the glycoprotein protein sequence of SARS-CoV-2 (the initial strain or the sequence with mutation(s) found in the SARS-CoV-2 variants) in order to test the efficacy of the drug or vaccine, or to find out the mutation(s) responsible for the change in efficacy of the drug or vaccine. Pseudoviruses are capable of replicating only once, while the SARS-CoV-2 virus and its variants are highly infectious. Therefore, pseudovirus is very much preferred to be used by laboratories which do not meet high biosafety level (BSL) requirements to do testing on the real virus.
References
1. P. Wang, M.S. Nair, L. Liu, et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature. 2021. PMID: 33684923
2. S.A. Madhi, V. Ballie, C.L. Cutland, et al. Efficacy of the ChAdOx1 nCoV-19 Covid-19 vaccine against the B.1.351 variant. NEJM, March 16, 2021. DOI: 10.1056/NEJMoa2102214
3. M. Voysey, S.A.C. Clemens, S.A. Madhi, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021 Jan 9;397(10269):99-111.
4. Novavax COVID-19 vaccine demonstrates 89.3% efficacy in UK Phase 3 trial. Novavax press release, Jan 28, 2021. https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3
5. Johnson & Johnson COVID-19 vaccine authorized by U.S. FDA for emergency use -- first single-shot vaccine in fight against global pandemic. J&J press release, February 27, 2021. https://www.jnj.com/johnson-johnson-covid-19-vaccine-authorized-by-u-s-fda-for-emergency-usefirst-single-shot-vaccine-in-fight-against-global-pandemic
In the last blog post, we’ve seen that the B.1.351 variant from South Africa is resistant to the antibodies in convalescent blood from most of the patients who have recovered from COVID-19, and it is also highly resistant to one of the currently-approved monoclonal antibody therapies to COVID-19. This blog post presents you with data on the efficacy of the vaccines that have been granted emergency use for COVID-19 in the UK, against the variant B.1.351.
B.1.351 is highly resistant to mRNA vaccines: Moderna mRNA-1273 and Pfizer BNT162b2
In order to check the efficacy of the mRNA vaccines to different variants, including variant B.1.351 and the original strain of SARS-CoV-2, researchers from Columbia University took blood samples from the volunteers who had received a complete course of either one of the two mRNA vaccines in the initial phase of clinical trials, mRNA-1273 from Moderna (12 participants) and Pfizer BNT162b2 (10 participants), and then performed neutralization tests* against the variants. The blood samples were collected at least 7 days after the last dose of vaccination in order to obtain serum with as high level of immunity as possible.1
They found that, when compared to the original strain, the overall neutralizing activity from the blood samples taken from the participants vaccinated with Moderna mRNA-1273 or with Pfizer BNT162b2, is significantly lower against the B.1.351 variant.1 According to this study, the overall neutralizing activity against B.1.351 was 12.4-fold lower than the original strain using blood samples from people vaccinated with Moderna mRNA-1273, and 10.3 fold lower using blood samples from people vaccinated with Pfizer BNT162b2.1
These results reflect the fact that while both the mRNA vaccines are highly protective against the original strain, they confer much weaker protection from infection by the B.1.351 variant. The people vaccinated with full course of either Moderna mRNA-1273 or Pfizer BNT162b2 still have a very high chance of being infected and getting sick even when high immunity from the vaccines is attained.
When the serum from vaccinated individuals was used to test against pseudoviruses with spike genes containing different mutations found in B.1.351, the researchers found that the E484K mutation confers the resistance to neutralization.1
AZD1222 has low efficacy towards B.1.351
A joint clinical trial study with scientists from the UK and South Africa showed that the efficacy of the two-dose regimen of adenovirus vaccine AZD1222 from AstraZeneca against B.1.351 was only 10.4%,2 whereas the efficacy of AZD1222 against the initial strain of SARS-CoV-2 can be as high as 90%.3
The study was conducted in South Africa between late June and early November last year, when the variant B.1.351 was emerging. It was a multi-centre, double-blind, randomized, controlled trial to assess the safety and efficacy of AZD1222 in people not infected with the human immunodeficiency virus (HIV). Adult participants below the age of 65 were assigned to receive two doses of vaccine or placebo 21 to 35 days apart.2 In the primary end-point analysis, 23 of 717 placebo recipients (3.2%) vs 19 of 750 vaccine recipients (2.5%) developed mild-to-moderate COVID-19, resulting in an efficacy of 21.9% from AZD1222.2
The efficacy result of AZD1222 from the clinical study in South Africa was very different from the previous report.3 However, sequencing analysis of the samples from the 42 participants with COVID-19 provided an explanation. It was found that 39 of the cases were caused by the B.1.351 variant. This led to the finding that vaccine efficacy against B.1.351 was only 10.4%. The study also found that incidence of serious adverse events was nearly equal between the vaccine and placebo groups.2
From this study, it was found that the adenovirus vaccine AZD1222 cannot very much protect vaccinated people against mild-to-moderate COVID-19 due to the B.1.351 variant.2
Conclusion
The B.1.351 South African strain emerged last August and has spread globally since then. Reports showed that the variant will not cause more serious illnesses and is not more deadly than the initial SARS-CoV-2 strain that causes COVID-19. Those people, such as the elderly and the ones with underlying health conditions, who are at high risk under the initial strain are at a similar risk level under the B.1.351 strain.
Although the South Africa variant B.1.351 has 50% higher transmissibility than the initial strain, we may not need to be too worried about the threat from this variant yet. B.1.1.7, one of the dominant strains in the UK, is also 50% higher in transmissibility than the initial strain, yet the COVID-19 infection rate and death toll in the UK is much lower than before. This means that variant strains even with higher transmissibility than the original strain can be contained, although it is not yet known for certain to what extent this containment was due to lockdowns (which will also apply to B.1.351) versus vaccines (which will not).
However, the concern is that the current therapies and vaccines designed against the original virus strain that cause COVID-19 will not work as well against the B.1.351 variant, as shown from the research studies presented in these two blog posts. Moreover, experience from clinical studies of COVID-19 vaccines in South Africa undertaken by Novavax, Janssen and Oxford/AstraZeneca also suggest that the variant B.1.351 can still cause infection even on the people who had been infected with the original strain of SARS-CoV-2. This shows that the immunity conferred from the previous infection by the original strain seems not strong enough to provide protection for the subsequent infection from the variant B.1.351.2,4,5
Therefore, until the B.1.351 variant is totally contained in the UK and/or an effective therapy or vaccine is available, we should stay cautious while the UK government is easing the lockdown restrictions.
*Neutralization is a process where the vaccine/monoclonal antibody acted against a pathogen, such as virus. A pathogen can be highly neutralized by vaccine/monoclonal antibody, which means its activity can be diminished or abolished by the vaccine/monoclonal antibody, i.e. the vaccine or monoclonal antibody is effective against the pathogen.
**Pseudovirus used in the experiments on SARS-CoV-2 refers to a retrovirus that is genetically engineered to carry the glycoprotein protein sequence of SARS-CoV-2 (the initial strain or the sequence with mutation(s) found in the SARS-CoV-2 variants) in order to test the efficacy of the drug or vaccine, or to find out the mutation(s) responsible for the change in efficacy of the drug or vaccine. Pseudoviruses are capable of replicating only once, while the SARS-CoV-2 virus and its variants are highly infectious. Therefore, pseudovirus is very much preferred to be used by laboratories which do not meet high biosafety level (BSL) requirements to do testing on the real virus.
References
1. P. Wang, M.S. Nair, L. Liu, et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature. 2021. PMID: 33684923
2. S.A. Madhi, V. Ballie, C.L. Cutland, et al. Efficacy of the ChAdOx1 nCoV-19 Covid-19 vaccine against the B.1.351 variant. NEJM, March 16, 2021. DOI: 10.1056/NEJMoa2102214
3. M. Voysey, S.A.C. Clemens, S.A. Madhi, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021 Jan 9;397(10269):99-111.
4. Novavax COVID-19 vaccine demonstrates 89.3% efficacy in UK Phase 3 trial. Novavax press release, Jan 28, 2021. https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3
5. Johnson & Johnson COVID-19 vaccine authorized by U.S. FDA for emergency use -- first single-shot vaccine in fight against global pandemic. J&J press release, February 27, 2021. https://www.jnj.com/johnson-johnson-covid-19-vaccine-authorized-by-u-s-fda-for-emergency-usefirst-single-shot-vaccine-in-fight-against-global-pandemic
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