Third COVID-19 Vaccine Dose Boosts Neutralising Antibodies in Poor Responders

ABSTRACTObjectiveTo determine if poor responders to COVID-19 RNA vaccines (<50% neutralisation) after two doses would remain poor responders, or if a third dose could elicit high levels of NAbs.DesignClinical follow-up studySettingAcademic and medical institutions in USAParticipants269 healthy individuals ranging in age from 19 to 80 (Average age = 51; 165 females and 104 males) who received either BNT162b2 (Pfizer) or mRNA1273 (Moderna) vaccines.Main Outcome MeasuresNAb levels were measured: i) 2-4 weeks after a second vaccine dose, ii) 2-4 months after the second dose, iii) within 1-2 weeks prior to a third dose and iv) 2-4 weeks after a third RNA vaccine dose.ResultsIn 269 study participants, percent neutralisation ranged from 0% to 99% 2-4 weeks after a second vaccine dose. The majority of vaccine recipients (154/269, 57%) demonstrated NAb levels at ≥75% 2-4 weeks after their second dose. Our study also revealed that 25% of vaccine recipients did not neutralise above 50% (Median neutralisation = 21%, titers <1:80) within a month after their second dose. We called these individuals “vaccine poor responders” (VPRs). Twenty-three VPRs ranging in age from 31 to 79 (10 males, 13 females, average age = 62.5) independently obtained a third dose of either BNT162b2 or mRNA-1273 vaccine 1-8 months (average = 5 months) after their second dose. Within a month after their third dose, poor responders showed an average 20-fold increase in NAb levels (range 46%-99%).ConclusionsThe results suggest that poor responders are not permanently poor responders; they can generate high NAb levels with an additional vaccine dose–independent of mRNA vaccine manufacturer. Previous reports indicate that NAb levels decline much more rapidly than clinical protection from hospitalisation and disease, but that does not account for vaccine recipients who never generated high levels of NAbs after two doses. It is possible that poor responders are a source of breakthrough infections. Although it is not known what levels of NAbs protect from infection or disease, many vaccine recipients in high-risk professions may wish to keep peripheral NAb levels high, limiting infection, asymptomatic viral replication, and potential transmission.