Home Medizin SARS-CoV-2-Infektionen und impfstoffinduzierte Antikörper lassen zunächst nach, stabilisieren sich jedoch für einen dauerhaften Schutz

SARS-CoV-2-Infektionen und impfstoffinduzierte Antikörper lassen zunächst nach, stabilisieren sich jedoch für einen dauerhaften Schutz

von NFI Redaktion

In a recent observational study published in the journal Immunity, researchers from the United States investigated the longevity of antibody responses to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and vaccination. They found that the humoral responses to SARS-CoV-2 infection and vaccination were long-lasting and biphasic, with an initial decline followed by stabilization after seven to nine months.

Study: Antibody responses induced by SARS-CoV-2 infections and vaccines are long-lasting, with an initial weakening phase followed by a stabilization phase. Kateryna Kon / Shutterstock

Background

The COVID-19 pandemic, which began four years ago, spurred the rapid development of messenger RNA (mRNA) vaccines, including BNT162b2 and mRNA-1273, which helped save millions of lives. However, emerging variants of SARS-CoV-2 and waning immunity against them present a challenge. While it is believed that immunity induced by mRNA-based vaccines rapidly declines, this perception is based on limited data, primarily from short-term studies.

Amid the exponential rise in SARS-CoV-2 cases in March 2020, the New York metropolitan region was in crisis, with frontline healthcare workers facing a high risk of infection. In response, a specific and sensitive SARS-CoV-2 enzyme immunoassay (ELISA) was developed, and the „Protection Associated with Rapid Immunity to SARS-CoV-2“ (PARIS) study was launched. This initiative tracked antibody responses, reinfection rates, and immunity factors among healthcare workers, providing crucial insights into pandemic dynamics. The researchers of the present study utilized data from the PARIS study, one of the most comprehensive investigations into the longevity of SARS-CoV-2 immunity, and analyzed humoral responses to SARS-CoV-2 infection and vaccination.

About the Study

The PARIS study was an observational longitudinal study conducted from April 2020 to March 2023, involving 501 healthcare workers. Their average age was 41 years, with 67% of them being female. Saliva samples were collected weekly in the first two months, and blood samples every two weeks. Nasopharyngeal/swab samples were taken in case of respiratory symptoms or after vaccination. About 38% of participants showed antibodies against SARS-CoV-2 spike-binding immunoglobulin G (IgG) at the beginning of the study. Overall, 93% of participants were vaccinated – 0.2% received four mRNA boosters, 2.6% received three boosters, 16.6% received two boosters, and 53.7% received one booster. Approximately 21.3% of participants chose not to receive a booster dose.

The study utilized REDCap for monthly surveys on general health status and SARS-CoV-2 risk, focusing on side effects following mRNA vaccinations and booster doses. Data from 228 participants were analyzed, and a severity assessment was conducted to uncover reported incidence and severity trends across doses and subgroups.

Serum antibody titers were determined using enzyme-linked immunosorbent assay (ELISA) and optical density at 490 nm (OD490). The statistical and quantitative analysis involved the use of Wilcoxon test, Mann-Whitney U test, Log-Rank test, Unweighted Pair Group Method with Arithmetic Mean (UPGMA) clustering, antibody kinetics modeling including nonlinear mixed-effects models (NLME), and demographic factor evaluation in post-vaccine and post-boost models.

Results and Discussion

While 38% of participants had detectable spike-binding IgG antibodies at the start of the study, 62% were seronegative at the initial visit. Vaccine-naive individuals showed low antibody titers after the first mRNA vaccine dose, with a significant increase after the second dose. However, individuals with pre-existing immunity reached higher and faster peak titers and retained more than three times higher responses after primary immunization.

Seven to nine months after primary immunization, antibody titers reached a stable state. Individuals with hybrid immunity retained higher and more stable titers compared to untreated recipients, indicating the induction of long-lasting serum antibodies. Additionally, the study found that vaccine type and age marginally influenced antibody titers in participants without hybrid immunity. According to the study, administration of booster doses raised the threshold at which long-term serum antibody responses reached a stable state.

During the study period, a total of 225 SARS-CoV-2 infections were observed, mostly occurring after vaccination, with breakthrough infections more common during the Omicron wave. In individuals with pure vaccine immunity, breakthrough infections acted as equivalent reinforcement of antibody responses, while in those with hybrid immunity, vaccination had a stronger enhancing effect compared to a second infection.

Participants with pre-existing immunity experienced more side effects after the first vaccine dose, with overall reactogenicity decreasing after subsequent doses. Booster doses caused fewer systemic side effects in naive participants compared to the second dose, while a different pattern emerged in participants with hybrid immunity, with slightly increased side effects with booster doses.

However, the study is limited by the inability to analyze mucosal immune responses, the lack of measuring neutralizing antibodies or antibodies against specific epitopes, and the absence of evaluating later variant spikes or nucleoproteins.

Conclusion

In conclusion, the present study provides evidence that antibody responses to SARS-CoV-2 mRNA vaccination exhibit a classic biphasic decline, transitioning from rapid decay to stabilization. The results underscore the longer protection conferred by hybrid immunity against multiple variants and the potential booster-like effect of breakthrough infections in strengthening immunity.

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