Characterization of the significant decline in humoral immune response six months post‐SARS‐CoV‐2 mRNA vaccination: A systematic review

Abstract

Accumulating evidence shows a progressive decline in the efficacy of coronavirus disease 2019 (COVID‐19) (severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2]) messenger RNA (mRNA) vaccines such as Pfizer‐BioNTech (mRNA BNT161b2) and Moderna (mRNA‐1273) in preventing breakthrough infections due to diminishing humoral immunity over time. Thus, this review characterizes the kinetics of anti‐SARS‐CoV‐2 antibodies after the second dose of a primary cycle of COVID‐19 mRNA vaccination. A systematic search of the literature was performed and a total of 18 articles ( N = 15 980 participants) were identified and reviewed. The percent difference of means of reported antibody titers was then calculated to determine the decline in humoral response after the peak levels postvaccination. Findings revealed that the peak humoral response was reached at 21–28 days after the second dose, after which serum levels progressively diminished at 4–6‐month postvaccination. Additionally, results showed that regardless of age, sex, serostatus, and presence of comorbidities, longitudinal data reporting antibody measurement exhibited a decline of both anti‐receptor binding domain immunoglobulin G (IgG) and anti‐spike IgG, ranging from 94% to 95% at 90–180 days and 55%–85% at 140–160 days, respectively, after the peak antibody response. This suggests that the rate of antibody decline may be independent of patient‐related factors and peak antibody titers but mainly a function of time and antibody class/molecular target. Hence, this study highlights the necessity of more efficient vaccination strategies to provide booster administration in attenuating the effects of waning immunity, especially in the appearance of new variants of concerns.

Serological Response and Relationship with Gender-Sensitive Variables among Healthcare Workers after SARS-CoV-2 Vaccination

“…Finally, antibody concentrations may not reflect cellular immune responses, which should be analyzed to fully evaluate the protection to COVID-19 [ 22 ]. However, anti-S IgG concentrations correlate with neutralizing antibodies concentrations and possibly with protective immunity [ 9 , 23 ].…”

SARS-CoV-2 spike protein antibody titers 6 months after SARS-CoV-2 mRNA vaccination among patients undergoing hemodialysis in Japan

“…Several types of vaccine against SARS-CoV-2 have been developed, of which mRNA vaccines are the most widely used because they can efficiently prevent severe illness, hospitalization, and death [ 1 , 2 ]. The mRNA vaccines are primarily administered in a two-dose schedule, but humoral immunity gradually declines, resulting in reduced protection against COVID-19 [ 3 , 4 ]. Therefore, a third booster vaccination has been administered in many countries [ 5 , 6 ].…”

Effect of Third and Fourth mRNA-Based Booster Vaccinations on SARS-CoV-2 Neutralizing Antibody Titer Formation, Risk Factors for Non-Response, and Outcome after SARS-CoV-2 Omicron Breakthrough Infections in Patients on Chronic Hemodialysis: A Prospective Multicenter Cohort Study

“…Therefore, we cannot comment on titer evolution in patients with third booster vaccinations who already had titers higher than 433 BAU/mL after the second dose. Nevertheless, one might speculate that repeat vaccinations may result in decreased waning of antibody titers as described in different other patient populations [ 25 ] and dialysis patients [ 26 , 27 ]. Despite rapid titer waning, Clarke et al were able to confirm a longstanding SARS-CoV-2 antigen–specific T-cell response in patients without detectable antibody titers six months post vaccination [ 28 ].…”