Duration of Heterotypic Protection Against SARS-CoV-2 Variants After Vaccination

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Researchers conducted a study to assess duration of functional humoral immunity against SARS-CoV-2 variants following COVID-19 vaccination.

Following COVID-19 mRNA vaccination, there may be increased susceptibility to SARS-CoV-2 variants of concern (VOC) due to decreased serum antibody and memory B cell (MBC) immune responses, according to results of a study published in The Journal of Infectious Disease.

Between January and June 2021, researchers conducted a longitudinal cohort study to assess functional humoral immunity and the reactivity of vaccine-induced MBC immune responses to SARS-CoV-2 VOCs up to 6 months following COVID-19 mRNA vaccination. The study included 17 healthy patients, of whom 15 were naïve to COVID-19 infection and 2 had recovered from a previous infection. At baseline, patients received either the BNT162b2 (n=14) or mRNA-1273 (n=3) COVID-19 vaccine. Blood sample specimens were collected from each patient prior to baseline, as well as 3 weeks after receipt of the first vaccine dose, and at 2 weeks and 6 months after receipt of the second vaccine dose.

Among patients included in the study, the median age was 41 (IQR, 24-54) years, 59% were women, and 94% were non-Hispanic White or Latino. Antibody titers were measured and the immune response of neutralizing antibodies were evaluated. The researchers found that neutralizing antibody activity increased significantly following each vaccine dose (P <.001; Effect Size [ES] >0.99). At 2 weeks and 6 months after receipt of the second COVID-19 vaccine dose, the researchers used the Spearman-Karber method to assess neutralizing antibody titers with values expressed as the dilution of sera required to reach the half-maximal neutralization dose (ND50). The median ND50 values were 3290 (IQR, 2572-4981) and 540 (IQR, 338-837) at 2 and 6 months, respectively, indicating a 6-fold decrease (P =.0001; ES =1.03).

The researchers assessed patients’ sera for vaccine-induced neutralizing antibodies with the ability to impair virus attachment and inhibit the interaction between human angiotensin-converting enzyme 2 (hACE2) and different receptor-binding domains (RBD) of the SARS-CoV-2 spike glycoprotein. Patients’ sera also were assessed for neutralization activity against several SARS-CoV-2 VOCs, with values expressed as the inverse dilution at which sera reached the half-maximal inhibitory dose (ID50). After patients received the second COVID-19 vaccine dose, the median ID50 values were 1198, 540, 333, 228, and 908 for the Wuhan-Hu-1 RDB, Alpha variant (B.1.1.7), Beta variant (B.1.1.7), Gamma variant (P.1), and Delta variant (B.1.617.2), respectively. Median ID50 values at 6 months were found to be 96, 52, 40, 29, and 94 for Wuhan-Hu-1 RBD and the Alpha, Beta, Gamma, and Delta SARS-CoV-2 variants, respectively. The researchers performed Wilcoxon signed rank testing and found that the mean ID50 values significantly increased for the Wuhan-Hu-1 RBD compared with the RBDs of the other SARS-CoV-2 VOCs. Compared with the median ID50 values at 2 weeks for the Wuhan-Hu-1 RBD and SARS-CoV-2 VOCs, there was a 7- to 12-fold decrease in median ID50 values at 6 months (P <.001).

This study was limited as whole spike-specific MBC responses and different MBC isotypes for each SARS-CoV-2 VOC were neither evaluated nor compared.

Although the findings showed that COVID-19 mRNA vaccination confers some protection against SARS-CoV-2 VoC, the researchers suggest that, “the [decreased] neutralizing antibody responses to some of the [SARS-CoV-2] variants could translate to an increased susceptibility to emerging SARS-CoV-2 variant strains in the face of waning immunity.”

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Haralambieva IH, Monroe JM, Ovsyannikova IG, Grill DE, Poland GA, Kennedy RB. Distinct homologous and variant-specific memory B-cell and antibody response over time after SARS-CoV-2 mRNA vaccination. J Infect Dis. Published February 8, 2022. doi:10.1093/infdis/jiac042