The COVID vaccination campaign has been extremely successful in the United States, with highly effective mRNA vaccines from Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273), as well as an Adenovirus-vectored vaccine from Janssen (Ad26.COV2.S). There are at least 2 questions to be answered. 1) While the vaccines seem to continue to work up to 6 months, how long will the efficacy last (hence the need for a booster)? and 2) how effective are these vaccines against the emerging variants (particularly against problematic B.1.351 and P.1 variants)? While antibodies produced from 2 doses of mRNA-1273 still seem to neutralize B.1.351 (first identified in South Africa) and P.1 (first identified in Brazil) variants, the neutralization capacity is reduced by 6.4- and 3.5-fold, respectively, which is concerning due to the possibility of breakthrough infection and waning efficacy.
There are 2 approaches to tackle this problem: 1) Administer a third booster of the original vaccine to increase the neutralization capacity and overcome the waning of antibodies, or 2) Administer a booster vaccine that matches the variant of concern (not the original vaccine).
In a pre-print paper (not peer-reviewed yet), Moderna shares the preliminary safety and immunogenicity results of a third booster shot in a phase 2 trial (http://doi.org/10.1101/2021.05.05.21256716). They enrolled adult participants from previous phase 2 or 3 trials who had received a 2-dose series of the original mRNA-1273 about 6-7 months before enrollment (no pregnant individuals). A booster dose of 50 mcg mRNA-1273 was given to 20 participants from the previous phase 2 trial. A booster dose of 50 mcg mRNA-1273.351 was given to 20 participants from the previous phase 3 trial. A 20 mg dose of mRNA-1273.351 is also being evaluated in 20 participants (results not published yet).
Boosting with mRNA-1273 resulted in a 23-, 32-, and 44-fold increase in neutralization against D614G (considered wild-type), B.1.351, and P.1 variants, respectively. Boosting with mRNA-1273.351 resulted in a 12-, 35-, and 27-fold increase in the neutralization of each variant, respectively. Of note, mRNA-1273.351 resulted in significantly higher titers against B.1.351 compared to mRNA-1273 boost. Because a correlate of protection from neutralizing antibodies has not been established yet, it remains to be seen if these boosted titers result in protection against B.1.351 and P.1 variants. The trial is ongoing and is currently evaluating a multivalent vaccine (50 mcg mRNA-1273.211) comprising of a 1:1 mix of the original mRNA-1273 (25 mcg) and mRNA-1273.351 (25 mcg). Will I personally get a third shot if authorized by the FDA? You bet! mRNA-1273.351.
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