COVID-19 Variants Raise New Questions About Vaccines

Although experts have begun warning that coronavirus disease 2019 (COVID-19) variants could soon become the dominant source of infections, the impact of these strains on vaccine efficacy and disease severity still leaves many questions unanswered.

The CDC has been conducting strain surveillance to better understand these variants and has found some concerning potential consequences. For example, there is evidence that the D614G mutation confers increased ability to spread more quickly.

Similarly, some variants may have the ability to evade detection by specific viral diagnostic tests. However, most commercial reverse-transcription polymerase chain reaction (RT-PCR)-based tests have multiple targets to detect the virus, so that even if a mutation impacts 1 of the targets, the other RT-PCR targets will still work.¹

Notably, the CDC said the ability to evade natural or vaccine-induced immunity could be the most concerning consequence. Once a large proportion of the population is vaccinated, experts say immune pressure could favor and accelerate the emergence of such variants by selecting for “escape mutants.” However, there is no evidence that this is currently happening, and most experts believe escape mutants are unlikely to emerge due to the nature of the virus.¹

So far, important variants include the United Kingdom (UK) variant, a South African variant, and a variant in Brazil. All 3 have been detected in the United States, with the UK variant found in December 2020 and the other 2 identified at the end of January 2021. According to the CDC, new information about the virologic, epidemiologic, and clinical characteristics is rapidly emerging.¹

The UK variant, called B.1.1.7, has a large number of mutations and may be associated with an increased risk of death, according to researchers in the UK. It is estimated to have first emerged in the UK in September 2020, with variants in the receptor binding domain (RBD) of the spike protein, 69/70 deletion, and a P681H mutation.

It is associated with more efficient and rapid transmission of the virus. Research on the risk of death is ongoing, although early reports found no evidence that the variant has any impact on disease severity or vaccine efficacy.¹

The variant found in South Africa, called B.1.351, has multiple variations in the spike protein, although it does not contain the deletion at 69/70 like the UK variant. It was first found in Nelson Mandela Bay, South Africa, in samples dating back to October 2020, and it appeared to be the dominant variant in Zambia in late December 2020.

There is currently no evidence to suggest that the variant has an impact on disease severity, although some evidence shows that the spike protein mutations E484K may affect neutralization by some polyclonal and monoclonal antibodies.¹

Finally, the P.1 variant found in Brazil contains 3 mutations in the spike protein receptor binding domain, including E484K. Some evidence suggests that the mutations in this variant may affect its transmissibility and antigenic profile, which could affect the ability of antibodies to recognize and neutralize the virus.¹

Both Pfizer and Moderna have presented research suggesting that their vaccines are effective against key mutations in the UK and South African variants. According to in vitro neutralization studies of sera from vaccinated individuals, a statement from Pfizer said their vaccine neutralized severe acute respiratory coronavirus 2 (SAR-CoV-2) with key mutations present in both the UK and South African variants.²

According to a press release, neutralization against the virus with the 3 key mutations found in the South African variant (E484K, N501Y, and D614G) was slightly lower compared to neutralization of the UK variant. However, the researchers believe the small differences in viral neutralization are unlikely to lead to a significant reduction in efficacy.²

Similarly, a study by Moderna showed no significant impact on neutralizing titers against the B.1.1.7 variant. A press release said the 2-dose regimen at the 100µg dose is expected to be protective against the emerging strains detected so far. Notably, however, the press release added that Moderna is developing an emerging variant booster candidate against the B.1.351 variant to determine whether it could be more effective.³

For this variant, the study found that vaccination produced neutralizing antibody titers that remain above the neutralizing titers shown to protect non-human primates against wildtype viral challenges, although there was a 6-fold reduction in neutralizing titers.³ Although they expect these levels of antibodies to offer protection, the observed reduction in titers could suggest a potential risk of earlier waning of immunity with the Moderna vaccine.³

“As we seek to defeat the COVID-19 virus, which has created a worldwide pandemic, we believe it is imperative to be proactive as the virus evolves. We are encouraged by these new data, which reinforce our confidence that the Moderna COVID-19 vaccine should be protective against these newly detected variants,” said Stephane Bancel, chief executive officer of Moderna, in a statement. “Out of an abundance of caution and leveraging the flexibility of our nRNA platform, we are advancing an emerging variant booster candidate against the variant first identified in the Republic of South Africa into the clinic to determine if it will be more effective to boost titers against this and potentially future variants.”³

REFERENCES

• Emerging SARS-CoV-2 Variants. CDC; Updated January 28, 2021. https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html. Accessed February 2, 2021.
• In Vitro Studies Demonstrate Pfizer and BioNTech COVID-19 Vaccine Elicits Antibodies That Neutralize SARS-CoV-2 With Key Mutations Present in UK And South African Variants [news release]. Pfizer; January 27, 2021. https://www.pfizer.com/news/press-release/press-release-detail/vitro-studies-demonstrate-pfizer-and-biontech-covid-19. Accessed February 2, 2021.
• Moderna COVID-19 Vaccine Retains Neutralizing Activity Against Emerging Variants First Identified in the UK and the Republic of South Africa [news release]. Moderna; January 25, 2021. https://investors.modernatx.com/news-releases/news-release-details/moderna-covid-19-vaccine-retains-neutralizing-activity-against. Accessed February 2, 2021.