Will the vaccines work against new variants?

A US government interagency group has developed a variant classification scheme that defines three classes of COVID-19 variants:

  • Variant of Interest
  • Variant of Concern
  • Variant of High Consequence

The B.1.1.7 (first detected in UK), B.1.351 (South Africa), P.1 (Brazil/Japan), B.1.427 (US-California), and B.1.429 (US-California) variants circulating in the United States are classified as variants of concern.  Currently, there are no variants of high consequence. For more information on the variants, visit the CDC website: https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html

Scientists are rushing to study the efficacy of the vaccines with these new variants. Most of the current vaccines appear to still be effective against the variants, though reduced efficacy was seen depending on the vaccine and the variant:

Pfizer-BioNTech:

  • In-vitro studies (using sera from vaccinated individuals to test new strains) on key mutations from the U.K and South African variants found that the vaccine-elicited antibodies, although with a reduced response to the South African variant.
  • In a study published February 17, the vaccine was found to have a 66% decrease in neutralization capabilities for the South African variant. However, it is unclear how this neutralization reduction will affect the efficacy of the vaccine.

Special Note: Reassuring news from data released on April 1: continued follow-up of the Pfizer  Phase 3 trial showed the vaccine is 100% effective in preventing COVID-19 cases in South Africa where the B.1.351 lineage is prevalent.

Moderna:

  • In-vitro studies found that the vaccine produced neutralizing titers against all key emerging variants tested, including B.1.1.7 and B.1.351, first identified in the UKand Republic of South Africa, respectively.
  • The study showed no significant impact on neutralizing titers against the B.1.1.7 variant relative to prior variants. A six-fold reduction in neutralizing titers was observed with the B.1.351 variant relative to prior variants. Despite this reduction, neutralizing titer levels with B.1.351 remain above levels that are expected to be protective.

Johnson & Johnson (clinical trial results)

  • 57% effective in preventing moderate to severe cases in South Africa, where the variant dominates; 89% effective in protecting against severe disease in all regions studied.
  • This vaccine was found to have similar efficacy for the U.K. variant than the original strain; however, in South Africa, it was found to have low efficacy for mild to moderate COVID-19, causing concerns that it is not effective against that variant; because the study was small and had young and healthy participants, it could not assess for efficacy against moderate to severe COVID-19.

AstraZeneca-Oxford

  • This vaccine was found to have similar efficacy for the U.K. variant than the original strain; however, in South Africa, it was found to have low efficacy for mild to moderate COVID-19, causing concerns that it is not effective against that variant; because the study was small and had young and healthy participants, it could not assess for efficacy against moderate to severe COVID-19.

Novavax

  • 89.3% efficacy in Phase 3 UK trial with over 50% of cases attributable to the now-predominant UK variant and the remainder attributable to COVID-19 virus.
  • 49.4% efficacy in total study population (60% efficacy in 94% of the study population that was HIV negative) was demonstrated in Phase 2b South Africa trial with over 90% of sequenced cases attributable to prevalent the South Africa variant.

Efforts are already being to understand how a vaccine booster or changes in the vaccine itself can target these new variants.

  • Moderna will be evaluating three approaches to booster vaccination:
    • A variant-specific booster candidate, mRNA-1273.351, based on the B.1.351 variant first identified in South Africa.
    • A multivalent booster candidate, mRNA-1273.211, which combines mRNA-1273, Moderna’s authorized vaccine against ancestral strains, and mRNA-1273.351 in a single vaccine.
    • A third dose of mRNA-1273, the authorized Moderna vaccine, as a booster.
  • Moderna also plans to evaluate the variant-specific mRNA-1273.351 and multivalent mRNA-1273.211 as a primary vaccination series for those who are seronegative. Participants will be evaluated in a two-dose series.
  • Trials in progress: Moderna is testing the above approaches in amendments to its phase 2 study; in parallel, NIH’s National Institute of Allergy and Infectious Disease, is leading a phase 1 trial.
  • Preclinical trial results: New preclinical data on Moderna’s variant-specific booster vaccine candidates is available:
    • These variant-specific vaccine candidates include mRNA-1273.351, which is more specifically targeted against the SARS-CoV-2 variant known as B.1.351 first identified in the Republic of South Africa, and a multivalent booster candidate, mRNA-1273.211, which combines mRNA-1273 (Moderna’s authorized vaccine against ancestral strains) and mRNA-1273.351 in a single vaccine.
    • Both mRNA-1273.351 and mRNA-1273.211 increase neutralizing titers against SARS-CoV-2 variants of concern in Balb/c mice. Specifically, this preclinical data confirms improved neutralizing titers with the mRNA-1273.351 vaccine primary series. The multi-valent vaccine provided the broadest level of immunity. A boost at 6 months with mRNA-1273.351 closed the neutralizing titer gap for the variants of concern. Following the mRNA-1273.351 boost, neutralizing titers were comparable between the ancestral strain (Wuhan) and the new B.1.351 variant.

Sources

CDC – Variants
NYT – Variant Tracker
Nature – Variants and Vaccines
Nature – Updating Vaccines
UK Report on New Variant
UK Second Report on New Variant
Moderna
Moderna Booster South Africa
Moderna Booster South Africa 2
Moderna Preclinical Trial Results for Variant
Pfizer
Pfizer – South African Variant
AstraZeneca-Oxford
Novavax
Johnson & Johnson
AMA: Podcast on Variants
Pfizer 6 Month Follow Up

Updated: April 14, 2021

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