Vaccine Efficacy Against Different SARS-CoV-2 Variants

The following article is an opinion piece written by Kevin Boyle. The views and opinions expressed in this article are those of the author and do not necessarily reflect the official position of Technology Networks.

Since the original SARS-CoV-2 strain emerged in 2019, many variants have been detected with their origins scattered across the world. Each new variant raises the same concerns for scientists: will this variant be more transmissible? Will the symptoms be more severe? Will the authorized vaccines still be effective?

Some variants have caused more concern than others and are accordingly named “variants of concern”. Currently, there are four in this category: alpha (B.1.1.7) (UK origin), beta (B.1.531) (South African origin), gamma (P.1) (Brazilian origin) and delta (B.1.617.2) (Indian origin). Until mid-May of this year, the alpha variant was dominant in the UK. Since then, the delta variant has taken over and spread at a worrying speed; as of mid-July, it accounted for approximately 99% of new cases. A similar pattern has emerged in the US, with the alpha and delta variants accounting for 80% of new infections (approximately 12% and 68% respectively). According to the World Health Organization (WHO), the delta variant has now spread to 135 countries.

Why are mutations concerning?

The mutations in the spike protein (S) of the SARS-CoV-2 virus that result in the different variants are well documented. It has also been established that the virus enters human cells via interaction with angiotensin-converting enzyme-2 (ACE-2) receptors on the cell surface. The mutations cause a stronger interaction between the virus and the receptor, promoting virus replication, leading to higher viral loads and increased transmission.

The delta variant has been causing the most recent concern. Dr. Mike Ryan, executive director, Health Emergencies program, said, “This particular delta variant is faster, it is fitter […] it is most lethal because it’s more efficient in the way it transmits between humans.” It is estimated that the delta variant has a 60% higher risk of transmission than the alpha variant, due to a mutation in the furin cleavage site, increasing the efficiency and quantity in which the virus enters cells. One study estimated that viral loads are up to 1000 times greater than for the alpha and beta variants. Similar viral loads were found for vaccinated and unvaccinated people for the delta variant. It has also been shown that the risk of hospitalization almost doubles for the delta variant versus the alpha variant, and those in hospital were likely to suffer from more severe symptoms.

The emerging data raises the question: how effective are the vaccines against the different variants, particularly the delta variant?

COVID-19 vaccine efficacy

There are 15 vaccines in use against SARS-CoV-2 worldwide, with the US and European countries predominantly using Moderna (mRNA-1273) and Pfizer (BNT162b2) (both mRNA based vaccines), AstraZeneca/Oxford (AZD1222) and Johnson & Johnson/Janssen (Ad26.cov2.S) (both adenovirus based vaccines).

The vaccine clinical trials were tested against the original strain of the virus. Since the emergence of the different variants, funding has been made available for urgent research to find out if vaccine efficacy changes against the variants. Research is ongoing, and the data from the studies are generally reported to show efficacy against symptomatic to moderate disease, and severe to critical disease or hospitalization, as summarized in Table 1. Depending on the study, there is variation in the efficacy values, which is reflected in the ranges shown. Not all of the data quoted are from peer reviewed publications and the authors point out that there are limitations in their studies. The studies also have varying conditions: when the study was carried out, the demographic covered, the number of participants and the length of time.

Table 1: The % efficacy of each of the authorized COVID-19 vaccines against variants, both in fighting symptomatic disease and hospitalization.^1-6

The data shows good protection against each variant, particularly against severe disease leading to hospitalization; even the lower efficacies listed are still above the 50% recommended by the World Health Organization. A drop-off in efficacy is seen with the different variants in comparison to the original strain, but not significantly. Encouragingly, the vaccines are proving to be effective against the delta variant.

The effectiveness of only one dose of either the Pfizer or AstraZeneca vaccine was low against the delta variant: 31-33% versus 49-50% against the alpha variant. However, after the recommended two doses, the efficacies were much higher and closer in value to the results against the alpha variant.

There are, however, some contradictory results. A very recent study in the US that compared the Pfizer and Moderna vaccines stated that the Pfizer vaccine efficacy against symptomatic disease dropped to 42% in July, a time when the delta variant became dominant. The Moderna vaccine performed much better (76% efficacy). Both vaccines were greater than 75% effective at preventing severe disease. The decrease in the efficacy of the Pfizer vaccine stated here is quite alarming and much greater than seen in the other studies.

Another contradiction: in February, this year, South Africa stopped its roll out of the AstraZeneca vaccine due to concerns relating to its efficacy against the beta variant that was prominent at the time. One very small study said the efficacy dropped to 10.4% against symptomatic disease, but research since has shown a much higher efficacy against this variant.

Our knowledge of short-term efficacy of the COVID-19 vaccines against variants continues to grow; but what about the long-term efficacy? It is a concern, and there is limited data available. One pre-print showed that the Pfizer vaccine efficacy dropped to 84% after six months, with the researchers stating an average decline of approximately 6% every two months. Moderna has said that, after six months, the efficacy of its vaccine remains between 94%-93%. However, both of these studies were conducted prior to the emergence and circulation of the delta variant.

It is possible that there will need to be a booster shot for the vaccines, but this is under debate. Dr. Laith Jamal Abu-Raddad from an immunology group in Qatar said, “I’m optimistic that vaccine immunity is going to last more than a few months and longer than a year, hopefully.” However, viral immunologist Dr. Mehul Suthar from Atlanta, Georgia said, “I’m a little concerned that the vaccines weren’t as robust in generating more durable antibody responses […] When you factor in variants, to me it’s clear that we’re going to need a booster.”

More research is clearly required, and over the coming months as data emerges, scientists will obtain a better idea of the most appropriate vaccine strategy.

References:

1. Nasreen S, He S, Chung H, et al. Effectiveness of COVID-19 vaccines against variants of concern, medRxiv. 2021. doi: 10.1101/2021.06.28.21259420.

2. Emary, KRW, Golubchik T, Aley, PK, et al. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-COV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial. TLancet. 2021; 397 (10282): 1351-1362. doi: 10.1016/S0140-6736(21)00628-0.

3. Thomas SJ, Moreira Jr ED, Kitchin N et al. Six month safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. medRxiv. 2021. doi: 10.1101/2021.07.28.21261159.

4. AstraZeneca. Vaxzevria is highly effective after one dose against severe disease or hospitalisation caused by Beta and Delta variants of concern. https://www.astrazeneca.com/media-centre/press-releases/2021/vaxzevria-is-highly-effective-after-one-dose-against-severe-disease-or-hospitalisation-caused-by-beta-and-delta-variants-of-concern.html. Published July 2021. Accessed August 7, 2021.

5. Charmet T, Schaeffer L, Grant R, et al. Impact of original, B.1.1.7, and B.1.351/P.1 SARS-CoV-2 lineages on vaccine effectiveness of two doses of COVID-19 mRNA vaccines: Results from a nationwide case-control study in France. Lancet Regional Health Europe. 2021; 8 (100171): 1-10. doi: 10.1016/j.lanepe.2021.100171.

6. Yale Medicine. Comparing the COVID-19 Vaccines: How Are They Different?  https://www.yalemedicine.org/news/covid-19-vaccine-comparison. Published August 2021. Accessed August 7, 2021.