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. 2022 Jul;94(7):2939-2961.
doi: 10.1002/jmv.27688. Epub 2022 Mar 9.

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

Kin Israel Notarte  1 , Israel Guerrero-Arguero  2 , Jacqueline Veronica Velasco  1 , Abbygail Therese Ver  1 , Maria Helena Santos de Oliveira  3 , Jesus Alfonso Catahay  1 , Md Siddiqur Rahman Khan  2 , Adriel Pastrana  1 , Grzegorz Juszczyk  4 , Jordi B Torrelles  2 , Giuseppe Lippi  5 , Luis Martinez-Sobrido  2 , Brandon Michael Henry  2
Affiliations

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

Kin Israel Notarte et al. J Med Virol. 2022 Jul.

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.

Keywords: COVID-19; Moderna; Pfizer-BioNTech; mRNA 1273; mRNA BNT162b2; vaccines.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Screening and appraisal of journal articles for inclusion in the systematic review
Figure 2
Figure 2
Kinetics of antibodies in studies reporting longitudinal data showing percentage decline from peak titer after vaccination for anti‐spike (A) and anti‐RBD (B) IgG antibodies. (C) Data summary of antibody percentage decline levels at 6‐month postvaccination. IgG, immunoglobulin G; RBD, receptor‐binding domain
Figure 3
Figure 3
Comparison by age of the percentage decline of anti‐SARS‐CoV‐2 antibodies by immunoglobulin class and target from peak to last measured timepoint in each study. SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2
Figure 4
Figure 4
Comparison by sex of the percentage decline of anti‐SARS‐CoV‐2 antibodies by immunoglobulin class and target from peak to last measured timepoint in each study. SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2
Figure 5
Figure 5
Comparison of antibody levels of seronegative and seropositive kinetics in studies reporting longitudinal data showing percentage decline from peak titer after vaccination. Red symbols indicate seronegative and green symbols indicate seropositive data
See this image and copyright information in PMC

References

    1. Albano PM, Notarte KI, Macaranas I, Maralit B. Cross‐contamination in molecular diagnostic laboratories in low‐ and middle‐income countries: a challenge to COVID‐19 testing. Philippine Journal of Pathology. 2020;5:7‐11. 10.21141/PJP.2020.09 - DOI
    1. Ciotti M, Ciccozzi M, Terrinoni A, Jiang WC, Wang C, , bin Bernardini S . The COVID‐19 pandemic. Crit Rev Clin Lab Sci. 2020;57(6):365‐388. 10.1080/10408363.2020.1783198 - DOI - PubMed
    1. Bergwerk M, Gonen T, Lustig Y, et al. Covid‐19 breakthrough Infections in vaccinated healthcare workers. N Engl J Med. 2021;385(16):1474‐1484. 10.1056/nejmoa2109072 - DOI - PMC - PubMed
    1. Lippi G, Henry BM, Plebani M. Anti‐sars‐cov‐2 antibodies testing in recipients of covid‐19 vaccination: why, when, and how? Diagnostics. 2021;11(6):1‐10. 10.3390/diagnostics11060941 - DOI - PMC - PubMed
    1. Lippi G, Henry BM, Plebani M. Optimizing effectiveness of COVID‐19 vaccination: will laboratory stewardship play a role? Clin Chem Lab Med. 2021;59(12):1885‐1888. 10.1515/cclm-2021-0972 - DOI - PubMed

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