Bates TA, McBride SK, Winders B, et al. - Waning of vaccine-induced antibody levels is hypothesized to be responsible for increasing reporting of breakthrough infections after vaccination against SARS-CoV-2. Herein researchers examined antibody levels and variant cross-neutralization after breakthrough infection.

• Participants were 26 fully vaccinated health care workers who were subsequently diagnosed with SARS-CoV-2 breakthrough infection; their mean age was 38 years; 20 [77%] were women; 24 [92%] were vaccinated with BNT162b2, sampled a median 28 days after PCR date and 213.5 days after final vaccination; 21 [81%] with mild symptoms.

• Participants were matched to 26 controls (mean age, 39 years; 21 [81%] women; 26 [100%] were vaccinated with BNT162b2, sampled a median 28 days after final vaccination).

• Ten cases were of Delta and nine were of non-Delta infections among sequence-confirmed breakthrough cases.

• Breakthrough infection was followed by a substantial boosting of humoral immunity, despite predominantly mild disease.

• Researchers identified the most notable boosting for IgA, possibly due to the differences in route of exposure between vaccination and natural infection.

• In addition, improved variant cross-neutralization was recorded in breakthrough sera, and Delta breakthrough infections in particular showed improved potency against Delta vs WA1, indicating the possible broadening in the protective immune response through development of variant boosters with antigenic inserts matching the emerging SARS-CoV-2 variants.