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) 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 (Severe Acute Respiratory Syndrome Coronavirus 2) antibodies after the second dose of a primary cycle of COVID-19 mRNA vaccination. A systematic search of literature was performed and a total of 18 studies (N=15,980) were identified and reviewed. The percent difference of means of reported antibody titers were then calculated to determine the decline in humoral response after the peak levels post-vaccination. 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 months post-vaccination. 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 (RBD) IgG and anti-spike IgG, ranging from 94-95% 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 (VoCs).

People with HIV receiving suppressive antiretroviral therapy show typical antibody durability after dual COVID-19 vaccination, and strong third dose responses

“…Our study confirms that antibody concentrations and neutralizing activities naturally decline following two-dose COVID-19 vaccination [31, 43]. Nevertheless, we found no evidence that PLWH receiving suppressive antiretroviral therapy exhibited lower antibody concentrations at any time point up to six months following two-dose vaccination, nor did they exhibit faster rates of antibody decline during this period compared to controls, after accounting for sociodemographic, health- and vaccine-related factors.…”

Effects of age, sex, serostatus, and underlying comorbidities on humoral response post-SARS-CoV-2 Pfizer-BioNTech mRNA vaccination: a systematic review

“…The third dose was also effective in reinforcing immunity against VoC [ 84 ]. Irrespective of the demographic or clinical conditions that would blunt the anti-SARS-CoV-2 antibody response, the importance of monitoring humoral immunity seems almost unquestionable for prioritizing vaccine boosters, including new vaccines able to efficiently protect against current and new SARS-CoV-2 VoC [ 85 ]. Their prioritized administration to especially vulnerable populations could provide the best compromise between limited vaccine availability and the highest clinical efficacy in averting or limiting SARS-CoV-2 infections and/or severe COVID-19 [ 86 ].…”

Durability of the immune response to a third BNT162b2 dose; five months follow-up

“…Two vaccine doses of BNT162b2 elicit a rapid induction of humoral response [22] followed by significant antibody waning [18,23,24], leading to approximately 30-and 6-fold lower IgG and neutralizing antibodies, respectively, six months after the second dose [18]. The superior humoral response following the third compared to the second dose resulted in an increase in not only the quantity (IgG levels) but, even more importantly, in the quality (avidity) of IgG antibodies [15].…”