In a recent pre-print study posted to the medRxiv* server, researchers analyzed the decline patterns of neutralizing antibodies following coronavirus disease 2019 (COVID-19) vaccination through a systematic literature review and meta-analysis.
Study: Waning of post-vaccination neutralizing antibody responses against SARS-CoV-2, a systematic literature review and meta-analysis. Image Credit: BaLL LunLa/Shutterstock.com
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Background
COVID-19 vaccines still effectively guard against severe illness and death caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, despite the constant evolution of the virus and the waning of acquired immunity.
However, these vaccines are less effective in preventing transmission, infection, and symptoms, especially against the Omicron variants. Immunity acquired from the vaccine or past infection does not fully protect against Omicron. Consequently, hybrid immunity, a mix of natural infection and vaccination-derived immunity, particularly with newer variants, is becoming more crucial.
While it is vital to study how new variants affect vaccine efficacy and the longevity of immunity, these studies take time. Lab results, like that of antibody tests, can be shared faster and might guide vaccine policies when clinical data is not available.
Yet, individual studies might not be comprehensive enough. Therefore, a meta-analysis that combines multiple studies offers a more powerful evaluation, assessing various factors like dosage and hybrid immunity benefits.
About the study
The present study performed a systematic review and meta-regression in line with the PRISMA guidelines.
The researchers searched PubMed, medRxiv, and bioRxiv between December 15, 2021, and January 31, 2023, focusing on the terms "COVID-19", "Omicron," and "neutralization." Reviewers examined titles, abstracts, and full texts, prioritizing studies with neutralization data against the Index and Omicron BA.1.
To thoroughly understand if booster doses or hybrid immunity influence neutralizing antibody waning rates, they executed meta-regressions studying changes in neutralization titers over time for specific strata.
The research incorporated studies detailing post-vaccine neutralizing antibody titers at multiple post-vaccination times. Selected pseudo-virus neutralization tests were utilized. Data was gathered from uninfected cohorts before initial or booster vaccinations and hybrid-immune groups after their first dose. Certain studies were omitted due to specific exclusion criteria.
The reliability of selected studies was methodically evaluated with a specialized tool they had crafted earlier for such studies. For the analysis, average decreases in geometric mean titers (GMTs) were deduced by specific factors like dose, prior infection status, and strain type.
They employed a series of mathematical and statistical processes, including calculations of logGMT, linear mixed-effects models, and regression analysis to conclude. Key results were then highlighted, with statistical significance at p < .05.
Study results
In the present study, of 8,418 articles screened, 26 were suitable for analysis. The analysis focused on five specific groups: 1) infection-naïve post-primary vaccinations against the Index strain; 2) infection-naïve post-boost vaccinations against the index; 3) infection-naive post-boost vaccinations against Omicron BA.1; 4) hybrid-immune post-primary vaccinations against the index; and 5) hybrid-immune post-primary vaccinations against Omicron BA.1.
Some cohorts did not have enough data for meta-analysis. All hybrid-immunity data was from pre-Omicron infections, limiting analysis of variant-specific impacts.
The studies displayed varied peak geometric mean titers (GMTs). For instance, messenger ribonucleic acid (mRNA)-boosted, infection-naive participants exhibited a range between 101 and 4,096 in GMTs. The highest average GMTs were seen in hybrid-immune post-primary participants against the Index strain, while the lowest was against Omicron variant BA.1 in infection-naive post-boost participants.
Generally, individuals with prior infections showed higher post-vaccination titers than those without, and Omicron BA.1 titers were lower than the Index strain. mRNA vaccines demonstrated significantly higher mean peak titers than other vaccines.
Neutralization rates decreased over six months across all groups. The waning rate within the first six months was consistent, though most cohorts provided limited data points. While neutralizing antibodies against Omicron BA.1 waned more than index-specific ones; differences were not statistically significant.
Regarding study reliability, only four out of 26 studies were deemed highly reliable. Poor reporting quality and assay standardization issues contributed to unclear or low-reliability scores. However, peak titers and waning rates didn't significantly differ between studies of varying reliability.
Discussion
The present study found a decline in neutralizing antibodies following COVID-19 vaccination over the first six months. The decline rates were relatively consistent regardless of whether individuals had a primary or booster dose or had previous infections.
Notably, the rate of antibody decline was more pronounced for the Omicron BA.1 variant than the original strain, although this was not statistically significant. Limited data on the effects of a second booster were available; preliminary findings suggest antibody longevity might be slightly better after the second booster.
Interestingly, three cohorts with a vector vaccine boost showcased the potential for longer-lasting antibody responses early post-immunization. Despite this, long-term studies showed consistent waning rates across all vaccine types. Combining mRNA and vector vaccines may offer heightened and durable immune responses.
Neutralizing antibodies are pivotal in protecting against mild and severe COVID-19 infection. Their levels can help predict vaccine effectiveness against various strains. Studies on newer Omicron subvariants have yielded mixed results on waning rates, underscoring the need for more research.
Significant differences were observed in overall antibody levels across different vaccine types, with mRNA vaccines showing higher titers. Despite varying initial levels, waning rates remained fairly consistent across vaccine platforms.
This suggests that those vaccinated with less effective primary regimens might reach non-protective antibody levels faster. The reliability of studies varied, with many having medium or low-reliability scores, mainly due to poor reporting standards.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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