Waning of Antibody Response Among Vaccinees who Received Two Doses of Covishield Vaccine.

Introduction: There are limited data available on the long-term presence of SARS-CoV-2-specific binding antibodies and neutralizing antibodies in circulation among the elderly population. This study aims to examine levels of anti-SARS-CoV-2 antibodies in vaccines who have completed at least 6 months since the second vaccine dose. A cross-sectional study was conducted from November 2021 to January 2022 among 199 vaccines aged 60 years and above residing in Belagavi city, who received two doses of the Covishield vaccine. Methods: Antibody response to SARS-COV-2 virus whole cell antigen was measured by a kit COVID KAWACH IgG Micro LISA (J Mitra and Company, India) in 199 participants who had completed at least 6 months after receiving the second dose of Covishield vaccine. The antibody response was measured as a ratio of optical density (OD) in the participant's sample to the mean OD in negative control test by normal (T/N). Independent Kruskal-Wallis test was applied to test the difference between the T/N ratio by months of vaccination since the second dose and by the age group strata. Results: The median T/N values among participants who completed 6, 7, 8, and 9 months since the second vaccine dose were 14.17, 10.46, 7.93, and 5.11, respectively, and this decline in T/N values was statistically significant. Antibody response values showed a decline with increasing age for participants in the age strata 60-69, 70-79, and 80 and above, respectively. Conclusions: A significant decline was observed in antibody response over 9 months supporting the administration of booster dose of vaccine.

Higher plasma levels of thymosin-α1 are associated with a lower waning of humoral response after COVID-19 vaccination: an eight months follow-up study in a nursing home.

BACKGROUND: Older people achieve lower levels of antibody titers than younger populations after Covid-19 vaccination and show a marked waning humoral immunity over time, likely due to the senescence of the immune system. Nevertheless, age-related predictive factors of the waning humoral immune response to the vaccine have been scarcely explored. In a cohort of residents and healthcare workers from a nursing home that had received two doses of the BNT162b2 vaccine, we measured specific anti-S antibodies one (T1), four (T4), and eight (T8) months after receiving the second dose. Thymic-related functional markers, including thymic output, relative telomere length, and plasma thymosin-α1 levels, as well as immune cellular subsets, and biochemical and inflammatory biomarkers, were determined at T1, and tested for their associations with the magnitude of the vaccine response (T1) and the durability of such response both, at the short- (T1-T4) and the long-term (T1-T8). We aimed to identify age-related factors potentially associated with the magnitude and persistence of specific anti-S immunoglobulin G (IgG)-antibodies after COVID-19 vaccination in older people. RESULTS: Participants (100% men, n = 98), were subdivided into three groups: young (< 50 years-old), middle-age (50-65 years-old), and older (≥65 years-old). Older participants achieved lower antibody titers at T1 and experienced higher decreases in both the short- and long-term. In the entire cohort, while the magnitude of the initial response was mainly associated with the levels of homocysteine [ß (95% CI); - 0.155 (- 0.241 to - 0.068); p = 0.001], the durability of such response at both, the short-term and the long-term were predicted by the levels of thymosin-α1 [- 0.168 (- 0.305 to - 0.031); p = 0.017, and - 0.123 (- 0.212 to - 0.034); p = 0.008, respectively]. CONCLUSIONS: Higher plasma levels of thymosin-α1 were associated with a lower waning of anti-S IgG antibodies along the time. Our results suggest that plasma levels of thymosin-α1 could be used as a biomarker for predicting the durability of the responses after COVID-19 vaccination, possibly allowing to personalize the administration of vaccine boosters.

Characterizing Longitudinal Antibody Responses in Recovered Individuals Following COVID-19 Infection and Single-Dose Vaccination: A Prospective Cohort Study.

BACKGROUND: Investigating antibody titers in individuals who have been both naturally infected with SARS-CoV-2 and vaccinated can provide insight into antibody dynamics and correlates of protection over time. METHODS: Human coronavirus (HCoV) IgG antibodies were measured longitudinally in a prospective cohort of qPCR-confirmed, COVID-19 recovered individuals (k = 57) in British Columbia pre- and post-vaccination. SARS-CoV-2 and endemic HCoV antibodies were measured in serum collected between Nov. 2020 and Sept. 2021 (n = 341). Primary analysis used a linear mixed-effects model to understand the effect of single dose vaccination on antibody concentrations adjusting for biological sex, age, time from infection and vaccination. Secondary analysis investigated the cumulative incidence of high SARS-CoV-2 anti-spike IgG seroreactivity equal to or greater than 5.5 log10 AU/mL up to 105 days post-vaccination. No re-infections were detected in vaccinated participants, post-vaccination by qPCR performed on self-collected nasopharyngeal specimens. RESULTS: Bivariate analysis (complete data for 42 participants, 270 samples over 472 days) found SARS-CoV-2 spike and RBD antibodies increased 14-56 days post-vaccination (p < 0.001) and vaccination prevented waning (regression coefficient, B = 1.66 [95%CI: 1.45-3.46]); while decline of nucleocapsid antibodies over time was observed (regression coefficient, B = -0.24 [95%CI: -1.2-(-0.12)]). A positive association was found between COVID-19 vaccination and endemic human ß-coronavirus IgG titer 14-56 days post vaccination (OC43, p = 0.02 & HKU1, p = 0.02). On average, SARS-CoV-2 anti-spike IgG concentration increased in participants who received one vaccine dose by 2.06 log10 AU/mL (95%CI: 1.45-3.46) adjusting for age, biological sex, and time since infection. Cumulative incidence of high SARS-CoV-2 spike antibodies (>5.5 log10 AU/mL) was 83% greater in vaccinated compared to unvaccinated individuals. CONCLUSIONS: Our study confirms that vaccination post-SARS-CoV-2 infection provides multiple benefits, such as increasing anti-spike IgG titers and preventing decay up to 85 days post-vaccination.

Longitudinal determination of BNT162b2 vaccine induced strongly binding SARS-CoV-2 IgG antibodies in a cohort of Romanian healthcare workers.

Mass vaccination against the disease caused by the novel coronavirus (COVID-19) was a crucial step in slowing the spread of SARS-CoV-2 in 2021. Even in the face of new variants, it still remains extremely important for reducing hospitalizations and COVID-19 deaths. In order to better understand the short- and long-term dynamics of humoral immune response, we present a longitudinal analysis of post-vaccination IgG levels in a cohort of 166 Romanian healthcare workers vaccinated with BNT162b2 with weekly follow-up until 35 days past the first dose and monthly follow-up up to 6 months post-vaccination. A subset of the patients continued with follow-up after 6 months and either received a booster dose or got infected during the Delta wave in Romania. Tests were carried out on 1694 samples using a CE-marked IgG ELISA assay developed in-house, containing S1 and N antigens of the wild type virus. Participants infected with SARS-CoV-2 before vaccination mount a quick immune response, reaching peak IgG levels two weeks after the first dose, while IgG levels of previously uninfected participants mount gradually, increasing abruptly after the second dose. Overall higher IgG levels are maintained for the previously infected group throughout the six month primary observation period (e.g. 36-65 days after the first dose, the median value in the previously infected group is 5.29 AU/ml, versus 3.58 AU/ml in the infection naïve group, p less than 0.001). The decrease of IgG levels is gradual, with lower median values in the infection naïve cohort even 7-8 months after vaccination, compared to the previously infected cohort (0.7 AU/ml versus 1.29 AU/ml, p = 0.006). Administration of a booster dose yielded higher median IgG antibody levels than post second dose in the infection naïve group and comparable levels in the previously infected group.

The allocation of COVID-19 vaccines and antivirals against emerging SARS-CoV-2 variants of concern in East Asia and Pacific region: A modelling study.

BACKGROUND: In view of emerging variants of concern (VOCs), we aimed to evaluate the impact of various allocation strategies of COVID-19 vaccines and antiviral such that the pandemic exit strategy could be tailored to risks and preferences of jurisdictions in the East Asia and Pacific region (EAP) to improve its efficiency and effectiveness. METHODS: Vaccine efficacies were estimated from the titre distributions of 50% plaque reduction neutralization test (PRNT50), assuming that PRNT50 titres of primary vaccination decreased by 2-10 folds due to antibody waning and emergence of VOCs, and an additional dose of vaccine would increase PRNT50 titres by 3- or 9-fold. We then used an existing SARS-CoV-2 transmission model to assess the outcomes of vaccine allocation strategies with and without the use of antivirals for symptomatic patients in Japan, Hong Kong, and Vietnam. FINDINGS: Increasing primary vaccination coverage was the most important contributing factor in reducing the total and peak number of COVID-19 hospitalisations, especially when population vaccine coverage or vaccine uptake among older adults was low. Providing antivirals to 50% of symptomatic infections only further reduced total and peak hospitalisations by 10-13%. The effectiveness of an additional dose of vaccine was highly dependent on the immune escape potential of VOCs and antibody waning, but less dependent on the boosting efficacy of the additional dose. INTERPRETATION: Increasing primary vaccination coverage should be prioritised in the design of allocation strategies of COVID-19 vaccines and antivirals against emerging VOCs, such as Omicron, in the EAP region. Heterologous vaccination with any available vaccine as the additional dose could be considered when planning pandemic exit strategies tailored to the circumstances of EAP jurisdictions. FUNDING: Health and Medical Research Fund, General Research Fund, AIR@InnoHK.

Evaluation of 2 commercial anti-SARS-CoV-2 antibody assays in an immunocompetent and immunocompromised inpatient population with COVID-19.

INTRODUCTION: During the COVID-19 pandemic, widespread introduction of SARS-CoV-2 antibody testing was introduced without a full understanding of the assays performance or the antibody kinetics following infection with SARS-CoV-2. METHODS: We performed an evaluation of 2 anti-SARS-CoV-2 antibody assays with a more detailed look into the effect of immune status on antibody sensitivity. RESULTS: Both assays demonstrated 100% specificity. The overall sensitivity of the Roche was 92.1% at ≥14 days and 94.8% at ≥21 days, and the overall sensitivity of the Abbott was 94.4% at ≥14 days and 98.2% at ≥21 days. 7/41 (17%) of patients included in this cohort were immunocompromised. Seroconversion was seen less commonly in the immunocompromised (4/7 [57.1%] seroconverted) and after excluding these patients 100% sensitivity was seen in both assays at ≥21 days. DISCUSSION: Performance of both assays in the immunocompetent appeared excellent after 21 days postsymptom onset. Both assays are highly specific.

SARS-CoV-2 antibody persistence in COVID-19 convalescent plasma donors: Dependency on assay format and applicability to serosurveillance.

BACKGROUND: Antibody response duration following severe acute respiratory syndrome coronavirus 2 infection tends to be variable and depends on severity of disease and method of detection. STUDY DESIGN AND METHODS: COVID-19 convalescent plasma from 18 donors was collected longitudinally for a maximum of 63-129 days following resolution of symptoms. All the samples were initially screened by the Ortho total Ig test to confirm positivity and subsequently tested with seven additional direct sandwich or indirect binding assays (Ortho, Roche, Abbott, Broad Institute) directed against a variety of antigen targets (S1, receptor binding domain, and nucleocapsid [NC]), along with two neutralization assays (Broad Institute live virus PRNT and Vitalant Research Institute [VRI] Pseudovirus reporter viral particle neutralization [RVPN]). RESULTS: The direct detection assays (Ortho total Ig total and Roche total Ig) showed increasing levels of antibodies over the time period, in contrast to the indirect IgG assays that showed a decline. Neutralization assays also demonstrated declining responses; the VRI RVPN pseudovirus had a greater rate of decline than the Broad PRNT live virus assay. DISCUSSION: These data show that in addition to variable individual responses and associations with disease severity, the detection assay chosen contributes to the heterogeneous results in antibody stability over time. Depending on the scope of the research, one assay may be preferable over another. For serosurveillance studies, direct, double Ag-sandwich assays appear to be the best choice due to their stability; in particular, algorithms that include both S1- and NC-based assays can help reduce the rate of false-positivity and discriminate between natural infection and vaccine-derived seroreactivity.

Intensified antibody response elicited by boost suggests immune memory in individuals administered two doses of SARS-CoV-2 inactivated vaccine.

Neutralizing antibodies in the subjects of an inactivated SARS-CoV-2 vaccine clinical trial showed a decreasing trend over months. An investigation studying the third immunization suggested that the waning of neutralizing antibodies in individuals administered two doses of inactivated vaccine does not mean the disappearance of immunity.