Contralateral second dose improves antibody responses to a 2-dose mRNA vaccination regimen.

BACKGROUNDVaccination is typically administered without regard to site of prior vaccination, but this factor may substantially affect downstream immune responses.METHODSWe assessed serological responses to initial COVID-19 vaccination in baseline seronegative adults who received second-dose boosters in the ipsilateral or contralateral arm relative to initial vaccination. We measured serum SARS-CoV-2 spike-specific Ig, receptor-binding domain-specific (RBD-specific) IgG, SARS-CoV-2 nucleocapsid-specific IgG, and neutralizing antibody titers against SARS-CoV-2.D614G (early strain) and SARS-CoV-2.B.1.1.529 (Omicron) at approximately 0.6, 8, and 14 months after boosting.RESULTSIn 947 individuals, contralateral boosting was associated with higher spike-specific serum Ig, and this effect increased over time, from a 1.1-fold to a 1.4-fold increase by 14 months (P < 0.001). A similar pattern was seen for RBD-specific IgG. Among 54 pairs matched for age, sex, and relevant time intervals, arm groups had similar antibody levels at study visit 2 (W2), but contralateral boosting resulted in significantly higher binding and neutralizing antibody titers at W3 and W4, with progressive increase over time, ranging from 1.3-fold (total Ig, P = 0.007) to 4.0-fold (pseudovirus neutralization to B.1.1.529, P < 0.001).CONCLUSIONSIn previously unexposed adults receiving an initial vaccine series with the BNT162b2 mRNA COVID-19 vaccine, contralateral boosting substantially increases antibody magnitude and breadth at times beyond 3 weeks after vaccination. This effect should be considered during arm selection in the context of multidose vaccine regimens.FUNDINGM.J. Murdock Charitable Trust, OHSU Foundation, NIH.

Immunogenicity of Pfizer mRNA COVID-19 Vaccination Followed by J&J Adenovirus COVID-19 Vaccination in Two Patients with Chronic Lymphocytic Leukemia.

Individuals with chronic lymphocytic leukemia (CLL) have significant immune disfunction, often further disrupted by treatment. While currently available COVID-19 vaccinations are highly effective in immunocompetent individuals, they are often poorly immunogenic in CLL patients. It is important to understand the role a heterologous boost would have in patients who did not respond to the initial two-dose mRNA vaccine series. SARS-CoV-2 specific immune responses, including antibodies and memory B-cells, CD4 and CD8 T-cells were assessed prior to vaccination, as well as postinitial vaccination series and post-third dose in two subjects. One subject seroconverted, had RBD-specific memory B-cells and spike-specific CD4 T-cells while the other did not. Both subjects had a spike-specific CD8 T-cell response after the original mRNA vaccination series that was further boosted after the third dose or remained stable. The results of this study, however small, are especially promising to CLL individuals who did not seroconvert following the initial mRNA vaccination series.