Anti-spike Antibodies Research Articles

Long-term dynamics of natural killer cells in response to SARS-CoV-2 vaccination: Persistently enhanced activity postvaccination.

Natural Killer (NK) cells play a significant role in the early defense against virus infections and cancer. Recent studies have demonstrated the involvement of NK cells in both the induction and effector phases of vaccine-induced immunity in various contexts. However, their role in shaping immune responses following SARS-CoV-2 vaccination remains poorly understood. To address this matter, we conducted a comprehensive analysis of NK cell phenotype and function in SARS-CoV-2 unexposed individuals who received the BNT162b2 vaccine. We employed a longitudinal study design and utilized a panel of 53 15-mer overlapping peptides covering the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein to assess NK cell function at 0 and 20 days following the first vaccine, and 30 and 240 days following booster. Additionally, we evaluated the levels of total IgG anti-Spike antibodies and their potential neutralizing ability. Our findings revealed an increased NK cell activity upon re-exposure to RBD when combined with IL12 and IL18 several months after booster. Concurrently, we observed that the frequencies of NKG2A + NK cells declined over the course of the follow-up period, while NKG2C increased only in CMV positive subjects. The finding that NK cell functions are inducible 9 months after vaccination upon re-exposure to RBD and cytokines, sheds light on the role of NK cells in contributing to SARS-CoV-2 vaccine-induced immune protection and pave the way to further studies in the field.

Anti-spike protein IgG antibody responses up to 3 months after the third dose of the BNT162b2 mRNA vaccine in medical care workers.

This study aimed to assess the changes in anti-spike protein IgG antibody titer over time following mRNA vaccination (BNT162b2) against severe acute respiratory syndrome coronavirus 2. We monitored IgG levels in 23 medical care workers (MCWs) for up to 3 months after administering the third dose of BNT162b2. Blood samples were periodically collected from all participants. Following the third dose, the median antibody titer increased to 252 and 327% compared with antibody levels at 1 and 3 months after the second dose, respectively. Additionally, compared with 1 month after the second dose, the median antibody titer decreased to 30.2 and 9.8% at 3 and 6 months, respectively, and to 39.1% at 3 months, compared with 1 month after the third dose. Antibody levels declined quickly after the second dose but declined more slowly after the third dose, showing a booster effect. This study provides insights into the immunogenicity of booster doses and time intervals for booster vaccination strategies.

No immunological interference or concerns about safety when seasonal quadrivalent influenza vaccine is co-administered with a COVID-19 mRNA-1273 booster vaccine in adults: A randomized trial

ABSTRACT The objective of the study was to assess the safety and immunogenicity of mRNA-1273 COVID-19 booster vaccination when co-administered with an egg-based standard dose seasonal quadrivalent influenza vaccine (QIV). This was a phase 3, randomized, open-label study. Eligible adults aged ≥ 18 years were randomly assigned (1:1) to receive mRNA-1273 (50 µg) booster vaccination and QIV 2 weeks apart (Seq group) or concomitantly (Coad group). Primary objectives were non-inferiority of haemagglutinin inhibition (HI) and anti-Spike protein antibody responses in the Coad compared to Seq group. 497/498 participants were randomized and vaccinated in the Seq/Coad groups, respectively. The adjusted geometric mean titer/concentration ratios (95% confidence intervals) (Seq/Coad) for HI antibodies were 1.02 (0.89–1.18) for A/H1N1, 0.93 (0.82–1.05) for A/H3N2, 1.00 (0.89–1.14] for B/Victoria, and 1.04 (0.93–1.17) for B/Yamagata; and 0.98 (0.84–1.13) for anti-Spike antibodies, thus meeting the protocol-specified non-inferiority criteria. The most frequently reported adverse events in both groups were pain at the injection site and myalgia. The 2 groups were similar in terms of the overall frequency, intensity, and duration of adverse events. In conclusion, co-administration of mRNA-1273 booster vaccine with QIV in adults was immunologically non-inferior to sequential administration. Safety and reactogenicity profiles were similar in both groups (clinicaltrials.gov NCT05047770).

Exploring cell-free assays for COVID-19 serosurvey

Serosurveys to monitor immunity toward COVID-19 in the population are primarily performed using an ELISA to screen samples for SARS-CoV-2 antibodies, followed by confirmation by a virus neutralization test, which is considered the Gold Standard. However, virus neutralization test may not be feasible for some laboratories because of the requirement for specific facilities and trained personnel. In an attempt to address this limitation, we evaluated three cell-free methods as potential alternatives for assessing SARS-CoV-2 seroprevalence in human population from plasma. We report the establishment of two inhibition ELISAs designed to detect anti-Spike RBD IgG antibodies and a microsphere quantitative suspension array technology assay, based on the Luminex xMAP platform, to measure the presence of antibodies against various SARS-CoV-2 antigens, including anti-RBD. These methods were also compared to a commercial chemiluminescent immunoassay designed for anti-RBD antibodies detection and to the combined ELISA + virus neutralization test strategy. These cell-free assays performed equally to estimate the percentage of positive and negative samples and could be used to determine the prevalence of SARS-CoV-2 antibodies in human population, at least in cohort with high-expected prevalence, without the use of seroneutralization assay.

Patient and Immunological Factors Associated With Delayed Clearance of Mucosal Severe Acute Respiratory Syndrome Coronavirus 2 RNA and Symptom Persistence.

Serial blood and mucosal samples were characterized for 102 participants enrolled a median of 7.0 days after coronavirus disease 2019 diagnosis. Mucosal RNA was detectable for a median of 31.5 (95% confidence interval [CI], 20.5-63.5) days, with persistence ≥1 month associated with obesity (body mass index [BMI] ≥30 kg/m2; odds ratio [OR], 3.9 [95% CI, 1.2-13.8]) but not age, sex, or chronic conditions. Fifteen participants had likely reinfection; lower serum anti-spike IgG levels were associated with reinfection risk. Nearly half of participants (47%) reported symptoms lasting ≥2-3 months; persistence ≥3 months was associated with BMI ≥30 kg/m2 (OR, 4.2 [95% CI, 1.1-12.8]) and peak anti-spike and anti-nucleocapsid antibody levels.

Efficacy of Preexposure Prophylaxis with Monoclonal Antibody Tixagevimab-Cilgavimab against Emerging SARS-CoV-2 Resistant Variants in Patients with Chronic Lymphocytic Leukemia

Introduction: Preexposure prophylaxis with monoclonal antibodies (mAbs) was developed in addition to COVID-19 vaccine for immunocompromised and those with insufficient immune response, among them patients with CLL. Omicron variant and its sublineages evolved mutations that escape mAbs neutralizing effect, yet the extent of which was not studied. Methods: We evaluated anti-spike titers and neutralization activity of COVID-19 wild-type (WT), Delta, Omicron, BA.2, BA.4, and BA.5 before and after tixagevimab-cilgavimab (TGM/CGM) dose of 150/150 mg or 300/300 mg in patients with CLL. Results: 70 patients were tested 2 weeks before and 4 weeks after receiving TGM/CGM mAbs. After TGM/CGM, anti-spike ab level increased 170-folds from 13.6 binding antibody unit (BAU)/mL (IQR, 0.4–288) to 2,328 BAU/mL (IQR, 1,681–3,500). Neutralization activity increased in all variants and was 176-folds higher in WT and 55-folds higher in Delta compared to 10-folds higher in Omicron and its sublineages (BA.2 ×11, BA.4 ×4, BA.5 ×18). Over follow-up period of 3 months, 20 patients (29%) with CLL acquired COVID-19 infection, all recovered uneventfully. In a multivariate analysis, anti-spike antibody titer was found a significant predictor for post-TGM/CGM COVID-19 infection. Conclusion: Efficacy of preexposure prophylaxis with TGM/CGM in patients with CLL is significantly reduced in era of Omicron and its sublineages BA.2, BA.4, and BA.5.

Single-center Outcomes After Liver Transplantation With SARS-CoV-2-Positive Donors: An Argument for Increased Utilization.

The COVID-19 pandemic has led to an increase in SARS-CoV-2-test positive potential organ donors. The benefits of life-saving liver transplantation (LT) must be balanced against the potential risk of donor-derived viral transmission. Although emerging evidence suggests that the use of COVID-19-positive donor organs may be safe, granular series thoroughly evaluating safety are still needed. Results of 29 consecutive LTs from COVID-19-positive donors at a single center are presented here. A retrospective cohort study of LT recipients between April 2020 and December 2022 was conducted. Differences between recipients of COVID-19-positive (n = 29 total; 25 index, 4 redo) and COVID-19-negative (n = 472 total; 454 index, 18 redo) deceased donor liver grafts were compared. COVID-19-positive donors were significantly younger (P = 0.04) and had lower kidney donor profile indices (P = 0.04) than COVID-19-negative donors. Recipients of COVID-19-positive donor grafts were older (P = 0.04) but otherwise similar to recipients of negative donors. Donor SARS-CoV-2 infection status was not associated with a overall survival of recipients (hazard ratio, 1.11; 95% confidence interval, 0.24-5.04; P = 0.89). There were 3 deaths among recipients of liver grafts from COVID-19-positive donors. No death seemed virally mediated because there was no qualitative association with peri-LT antispike antibody titers, post-LT prophylaxis, or SARS-CoV-2 variants. The utilization of liver grafts from COVID-19-positive donors was not associated with a decreased overall survival of recipients. There was no suggestion of viral transmission from donor to recipient. The results from this large single-center study suggest that COVID-19-positive donors may be used safely to expand the deceased donor pool.

Factors influencing adverse events following COVID-19 vaccination

ABSTRACT Various novel platform technologies have been used for the development of COVID-19 vaccines. In this nested cohort study among healthcare workers in Australia and Brazil who received three different COVID-19-specific vaccines, we (a) evaluated the incidence of adverse events following immunization (AEFI); (b) compared AEFI by vaccine type, dose and country; (c) identified factors influencing the incidence of AEFI; and (d) assessed the association between reactogenicity and vaccine anti-spike IgG antibody responses. Of 1302 participants who received homologous 2-dose regimens of ChAdOx1-S (Oxford-AstraZeneca), BNT162b2 (Pfizer-BioNTech) or CoronaVac (Sinovac), 1219 (94%) completed vaccine reaction questionnaires. Following the first vaccine dose, the incidence of any systemic reaction was higher in ChAdOx1-S recipients (374/806, 46%) compared with BNT162b2 (55/151, 36%; p = 0.02) or CoronaVac (26/262, 10%; p < 0.001) recipients. After the second vaccine dose, the incidence of any systemic reaction was higher in BNT162b2 recipients (66/151, 44%) compared with ChAdOx1-S (164/806, 20%; p < 0.001) or CoronaVac (23/262, 9%; p < 0.001) recipients. AEFI risk was higher in younger participants, females, participants in Australia, and varied by vaccine type and dose. Prior COVID-19 did not impact the risk of AEFI. Participants in Australia compared with Brazil reported a higher incidence of any local reaction (170/231, 74% vs 222/726, 31%, p < 0.001) and any systemic reaction (171/231, 74% vs 328/726, 45%, p < 0.001), regardless of vaccine type. Following a primary course of ChAdOx1-S or CoronaVac vaccination, participants who did not report AEFI seroconverted at a similar rate to those who reported local or systemic reactions. In conclusion, we found that the incidence of AEFI was influenced by participant age and COVID-19 vaccine type, and differed between participants in Australia and Brazil.

A Dried Blood Spot protocol for high-throughput quantitative analysis of SARS-CoV-2 RBD serology based on the Roche Elecsys system.

SARS-CoV-2 spreads pandemically since 2020; in 2021, effective vaccinations became available and vaccination campaigns commenced. Still, it is hard to track the spread of the infection or to assess vaccination success in the broader population. Measuring specific anti-SARS-CoV-2 antibodies is the most effective tool to track the spread of the infection or successful vaccinations. The need for venous-blood sampling however poses a significant barrier for large studies. Dried-blood-spots on filter-cards (DBS) have been used for SARS-CoV-2 serology in our laboratory, but so far not to follow quantitative SARS-CoV-2 anti-spike reactivity in a longitudinal cohort. We developed a semi-automated protocol or quantitative SARS-CoV-2 anti-spike serology from self-sampled DBS, validating it in a cohort of matched DBS and venous-blood samples (n = 825). We investigated chromatographic effects, reproducibility, and carry-over effects and calculated a positivity threshold as well as a conversion formula to determine the quantitative binding units in the DBS with confidence intervals. Sensitivity and specificity reached 96.63% and 97.81%, respectively, compared to the same test performed in paired venous samples. Between a signal of 0.018 and 250 U/mL, we calculated a correction formula. Measuring longitudinal samples during vaccinations, we demonstrated relative changes in titers over time in several individuals and in a longitudinal cohort over four follow-ups. DBS sampling has proven itself for anti-nucleocapsid serosurveys in our laboratory. Similarly, anti-spike high-throughput DBS serology is feasible as a complementary assay. Quantitative measurements are accurate enough to follow titer dynamics in populations also after vaccination campaigns. This work was supported by the Bavarian State Ministry of Science and the Arts; LMU University Hospital, LMU Munich; Helmholtz Center Munich; University of Bonn; University of Bielefeld; German Ministry for Education and Research (proj. nr.: 01KI20271 and others) and the Medical Biodefense Research Program of the Bundeswehr Medical Service. Roche Diagnostics provided kits and machines for analyses at discounted rates. The project is funded also by the European-wide Consortium ORCHESTRA. The ORCHESTRA project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 101016167. The views expressed in this publication are the sole responsibility of the author, and the Commission is not responsible for any use that may be made of the information it contains.IMPORTANCESARS-CoV-2 has been spreading globally as a pandemic since 2020. To determine the prevalence of SARS-CoV-2 antibodies among populations, the most effective public health tool is measuring specific anti-SARS-CoV-2 antibodies induced by infection or vaccination. However, conducting large-scale studies that involve venous-blood sampling is challenging due to the associated feasibility and cost issues. A more cost-efficient and less invasive method for SARS-CoV-2 serological testing is using Dried-Blood-Spots on filter cards (DBS). In this paper, we have developed a semi-automated protocol for quantifying SARS-CoV-2 anti-spike antibodies from self-collected DBS. Our laboratory has previously successfully used DBS sampling for anti-nucleocapsid antibody surveys. Likewise, conducting high-throughput DBS serology for anti-spike antibodies is feasible as an additional test that can be performed using the same sample preparation as the anti-nucleocapsid analysis. The quantitative measurements obtained are accurate enough to track the dynamics of antibody levels in populations, even after vaccination campaigns.

High pre-Delta and early-Omicron SARS-CoV-2 seroprevalence detected in dried blood samples from Kinshasa (D.R. Congo).

Studies on the impact of the COVID-19 pandemic in sub-Saharan Africa have yielded varying results, although authors universally agree the real burden surpasses reported cases. The primary objective of this study was to determine SARS-CoV-2 seroprevalence among patients attending Monkole Hospital in Kinshasa (D.R. Congo). The secondary objective was to evaluate the analytic performance of two chemiluminescence platforms: Elecsys® (Roche) and VirClia® (Vircell) on dried blood spot samples (DBS). The study population (N = 373) was recruited in two stages: a mid-2021 blood donor cohort (15.5% women) and a mid-2022 women cohort. Crude global seroprevalence was 61% (53.9%-67.8%) pre-Delta in 2021 and 90.2% (84.7%-94.2%) post-Omicron in 2022. Anti-spike (S) antibody levels significantly increased from 53.1 (31.8-131.3) U/mL in 2021 to 436.5 (219.3-950.5) U/mL in 2022 and were significantly higher above 45 years old in the 2022 population. Both platforms showed good analytic performance on DBS samples: sensitivity was 96.8% for IgG (antiN/S) (93.9%-98.5%) and 96.0% (93.0%-98.0%) for anti-S quantification. These results provide additional support for the notion that exposure to SARS-CoV-2 is more widespread than indicated by case-based surveillance and will be able to guide the pandemic response and strategy moving forward. Likewise, this study contributes evidence to the reliability of DBS as a tool for serological testing and diagnosis in resource-limited settings.

Intradermal delivery of the third dose of the mRNA-1273 SARS-CoV-2 vaccine: safety and immunogenicity of a fractional booster dose

ObjectivesThe aim of this study was to assess the safety and immunogenicity of a dose-sparing fractional intradermal (ID) booster strategy with the mRNA-1273 COVID-19 vaccine. MethodsCOVID-19 naive adults aged 18–30 years were recruited from a previous study on primary vaccination regimens that compared 20 μg ID vaccinations with 100 μg intramuscular (IM) vaccinations with mRNA-1273 as the primary vaccination series. Participants previously immunized with ID regimens were randomly assigned (1:1) to receive a fractional ID booster dose (20 μg) or the standard-of-care intramuscular (IM) booster dose (50 μg) of the mRNA-1273 vaccine, 6 months after completing their primary series (ID-ID and ID-IM group, respectively). Participants that had received a full dose IM regimen as the primary series, received the IM standard-of-care booster dose (IM-IM group). In addition, COVID-19 naive individuals aged 18–40 years who had received an IM mRNA vaccine as the primary series were recruited from the general population to receive a fractional ID booster dose (IM-ID group). Immunogenicity was assessed using IgG anti-spike antibody responses and neutralizing capacity against SARS-CoV-2. Cellular immune responses were measured in a sub-group. Safety and tolerability were monitored. ResultsIn January 2022, 129 participants were included in the study. Fractional ID boosting was safe and well tolerated, with fewer systemic adverse events compared with IM boosting. At day 28 post-booster, anti-spike S1 IgG geometric mean concentrations were 9106 (95% CI, 7150–11 597) binding antibody units (BAU)/mL in the IM-IM group and 4357 (3003–6322) BAU/mL; 6629 (4913–8946) BAU/mL; and 5264 (4032–6873) BAU/mL in the ID-IM, ID-ID, and IM-ID groups, respectively. DiscussionIntradermal boosting provides robust immune responses and is a viable dose-sparing strategy for mRNA COVID-19 vaccines. The favourable side-effect profile supports its potential to reduce vaccine hesitancy. Fractional dosing strategies should be considered early in the clinical development of future mRNA vaccines to enhance vaccine availability and pandemic preparedness.

Strong humoral response after Covid-19 vaccination correlates with the common HLA allele A*03:01 and protection from breakthrough infection.

Few data exist on the role of genetic factors involving the HLA system on response to Covid-19 vaccines. Moving from suggestions of a previous study investigating the association of some HLA alleles with humoral response to BNT162b2, we here compared the HLA allele frequencies among weak (n = 111) and strong (n = 123) responders, defined as those healthcare workers with the lowest and the highest anti-Spike antibody levels after vaccination. Individuals with clinical history of Covid-19 or positive anti-nucleocapside antibodies were excluded. We found the common HLA-A*03:01 allele as an independent predictor of strong humoral response (OR = 12.46, 95% CI: 4.41-35.21, p < 0.0001), together with younger age of vaccines (p = 0.004). Correlation between antibody levels and protection from breakthrough infection has been observed, with a 2-year cumulative incidence of 42% and 63% among strong and weak responders, respectively (p = 0.03). Due to the high frequency of HLA-A*03:01 and the need for seasonal vaccinations against SARS-CoV-2 mutants, our findings provide useful information about the inter-individual differences observed in humoral response after Covid-19 vaccine and might support further studies on the next seasonal vaccines.

Immunogenicity of SARS-CoV-2 vaccines BBV152 (COVAXIN®) and ChAdOx1 nCoV-19 (COVISHIELD™) in seronegative and seropositive individuals in India: a multicentre, nonrandomised observational study

There are limited global data on head-to-head comparisons of vaccine platforms assessing both humoral and cellular immune responses, stratified by pre-vaccination serostatus. The COVID-19 vaccination drive for the Indian population in the age group 18-45 years began in April 2021 when seropositivity rates in the general population were rising due to the delta wave of COVID-19 pandemic during April-May2021. Between June 30, 2021, and Jan 28, 2022, we enrolled 691 participants in the age group 18-45 years across four clinical sites in India. In this non-randomised and laboratory blinded study, participants received either two doses of Covaxin® (4 weeks apart) or two doses of Covishield™ (12 weeks apart) as per the national vaccination policy. The primary outcome was the seroconversion rate and the geometric mean titre (GMT) of antibodies against the SARS-CoV-2 spike and nucleocapsid proteins post two doses. The secondary outcome was the frequency of cellular immune responses pre- and post-vaccination. When compared to pre-vaccination baseline, both vaccines elicited statistically significant seroconversion and binding antibody levels in both seronegative and seropositive individuals. In the per-protocol cohort, Covishield™ elicited higher antibody responses than Covaxin® as measured by seroconversion rate (98.3% vs 74.4%, p<0.0001 in seronegative individuals; 91.7% vs 66.9%, p<0.0001 in seropositive individuals) as well as by anti-spike antibody levels against the ancestral strain (GMT 1272.1 vs 75.4 binding antibody units/ml [BAU/ml], p<0.0001 in seronegative individuals; 2089.07 vs 585.7 BAU/ml, p<0.0001 in seropositive individuals). As participants at all clinical sites were not recruited at the same time, site-specific immunogenicity was impacted by the timing of vaccination relative to the delta and omicron waves. Surrogate neutralising antibody responses against variants-of-concern including delta and omicron was higher in Covishield™ recipients than in Covaxin® recipients; and in seropositive than in seronegative individuals after both vaccination and asymptomatic infection (omicron variant). T cell responses are reported from only one of the four site cohorts where the vaccination schedule preceded the omicron wave. In seronegative individuals, Covishield™ elicited both CD4+ and CD8+ spike-specific cytokine-producing T cells whereas Covaxin® elicited mainly CD4+ spike-specific T cells. Neither vaccine showed significant post-vaccination expansion of spike-specific T cells in seropositive individuals. Covishield™ elicited immune responses of higher magnitude and breadth than Covaxin® in both seronegative individuals and seropositive individuals, across cohorts representing the pre-vaccination immune history of most of the vaccinated Indian population. Corporate social responsibility (CSR) funding from Hindustan Unilever Limited (HUL) and Unilever India Pvt. Ltd. (UIPL).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response in adults with predominantly antibody deficiency

Patients with predominantly antibody deficiency (PAD) have lower anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibody levels after initial 2-dose SARS-CoV-2 vaccination than healthy controls do; however, the anti-spike antibody responses and neutralization function in patients with PAD following subsequent immunizations remain understudied. We sought to characterize anti-spike antibody responses in adults with PAD over the course of 5 SARS-CoV-2 vaccine doses and identify diagnostic and immunophenotypic risk factors for low antibody response. We evaluated anti-spike antibody levels in 117 adult patients with PAD and 192 adult healthy controls following a maximum of 5 SARS-CoV-2 immunizations. We assessed neutralization of the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant and analyzed infection outcomes. The patients with PAD had significantly lower mean anti-spike antibody levels after 3 SARS-CoV-2 vaccine doses than the healthy controls did (1,439.1 vs 21,890.4 U/mL [P< .0001]). Adults with secondary PAD, severe primary PAD, and high-risk immunophenotypes had lower mean anti-spike antibody levels following vaccine doses 2, 3, and/or 4 but not following vaccine dose 5. Compared with patients with mild and moderate PAD, patients with severe PAD had a higher rate of increase in anti-spike antibody levels over 5 immunizations. Astrong positive correlation was observed between anti-spike antibody levels and neutralization of both the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant. Most infections were managed on an outpatient basis. In all of the patients with PAD, anti-spike antibody levels increased with successive SARS-CoV-2 immunizations and were correlated with neutralization of both the SARS-CoV-2 wild-type strain and the Omicron BA.5 variant. Secondary PAD, severe primary PAD, and high-risk immunophenotypes were correlated with lower mean anti-spike antibody levels following vaccine doses 2 through 4. Patients with severe PAD had the highest rate of increase in anti-spike antibody levels over 5 immunizations. These data suggest a clinical benefit to sequential SARS-CoV-2 immunizations, particularly among high-risk patients with PAD.

Anti-nucleocapsid antibody levels following initial and repeat SARS-CoV-2 infections in a cohort of long-term care facility residents in England (VIVALDI).

We have previously demonstrated that older residents of long-term care facilities (LTCF) in the UK show levels of anti-spike antibodies that are comparable to the general population following primary series and booster vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, data on the humoral response to other SARS-CoV-2 proteins associated with natural infection are scarce in this vulnerable population. We measured quantitative levels of anti-nucleocapsid antibodies in blood samples taken from LTCF residents and staff after initial and repeat SARS-CoV-2 infections, between December 2020 and March 2023. Data on SARS-CoV-2 infection and vaccination were obtained through linkage to national datasets. Linear mixed effects models were used to investigate anti-nucleocapsid antibody levels, using log10 scale, in relation to time from most recent infection. This included evaluation of associations between repeat infection, staff/resident status, age, sex, Omicron infection and vaccination history and peak antibody level and slope of decline with time. We analysed 405 antibody observations from 220 residents and 396 observations from 215 staff. Repeat infection was associated with 8.5-fold (95%CI 4.9-14.8-fold) higher initial (peak) median anti-nucleocapsid antibody level, with steeper subsequent slope of decline. There were no significant differences in antibody level associated with resident (vs. staff) status or age, but Omicron infection was associated with 3.6-fold (95%CI 2.4-5.4-fold) higher levels. There was stronger evidence of waning of antibody levels over time in a sensitivity analysis in which observations were censored in cases with suspected undetected repeat infection. We found similar levels of anti-nucleocapsid antibody in residents and staff of LTCFs. Repeat infection and infection with an Omicron strain were associated with higher peak values. There was evidence of waning of anti-nucleocapsid antibody levels over time.

An epidemiological survey of COVID-19 serology and its association with clinical infection among older adults– does antibody titer matter?

BackgroundOlder adults are at increased risk of severe SARS-CoV-2 infection. In this study we assessed the response to COVID-19 vaccination and infection rates among nursing homes (NH) and assisted-living care home (ALCH) residents.MethodsThe study was conducted between August 2021 and January 2022, after widespread population vaccination with the third dose of Pfizer-BioNtech mRNA COVID-19 vaccine in Israel. Three groups were addressed: hospitalized older patients; NH and ALCH residents. Demographic data, COVID-19 serology (anti-spike IgG antibodies) and PCR test results were obtained to assess the dynamics of antibody titers and its correlation to infection rates.ResultsTwo-hundred eighty-five individuals were evaluated; 92 hospitalized patients; 100 ALCH residents and 93 NH residents. In the latter two groups two serology surveys were conducted three months apart. Hospitalized patients were younger than ALCH and NH residents (mean age 80.4 ± 8 versus 82.6 ± 8 and 83.6 ± 5, respectively, p = 0.01), and had more comorbidities (p = 0.003). The degree of decline in the antibody level overtime was similar in ALCH and NH residents. Infection rates were higher among NH residents than ALCH residents [35/91 (38.4%) versus 11/100 (11%), p < 0.001]. Antibody level was lower among those infected [2113 (1271–3512) Au/ml versus 4113 (3364–5029) Au/ml, p < 0.001]. Adjusted analysis showed that NH residence, but not antibody levels, were significantly associated with infection.ConclusionAmong older adults, infection rates inversely correlated with antibody level. However, only nursing home residence was significantly associated with infection, suggesting that other factors such as crowding considerably contribute to the risk of infection.

Deficient Generation of Spike-Specific Long-Lived Plasma Cells in the Bone Marrow After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Generation of a stable long-lived plasma cell (LLPC) population is the sine qua non of durable antibody responses after vaccination or infection. We studied 20 individuals with a prior coronavirus disease 2019 infection and characterized the antibody response using bone marrow aspiration and plasma samples. We noted deficient generation of spike-specific LLPCs in the bone marrow after severe acute respiratory syndrome coronavirus 2 infection. Furthermore, while the regression model explained 98% of the observed variance in anti-tetanus immunoglobulin G levels based on LLPC enzyme-linked immunospot assay, we were unable to fit the same model with anti-spike antibodies, again pointing to the lack of LLPC contribution to circulating anti-spike antibodies.

Impact of Antenatal SARS-CoV-2 Exposure on SARS-CoV-2 Neutralization Potency.

A pregnancy booster dose significantly reduces the risk and severity of COVID-19, and it is widely recommended. A prospective cohort study was conducted to compare the transplacental passage of maternal antibodies from vaccination or infection during three trimesters against both the vaccine-targeted Wuhan strain and the Omicron strain of SARS-CoV-2. Maternal-infant dyads from vaccinated mothers were collected between 6 June 2022 and 20 September 2022. We analyzed 38 maternal-infant dyads from mothers who had been infected with COVID-19 and 37 from mothers without any previous infection. Pregnant women who received their last COVID-19 vaccine dose in the third trimester exhibited the highest anti-spike protein antibody levels and neutralizing potency against both the Wuhan strain and Omicron BA.2 variant in their maternal and cord plasma. Both second- and third-trimester vaccination could lead to a higher level of neutralization against the Wuhan and Omicron strains. COVID-19 infection had a negative effect on the transplacental transfer ratio of SARS-CoV-2 antibodies. A booster dose during the second or third trimester is encouraged for the maximum transplacental transfer of humoral protection against COVID-19 for infants.

Dynamics of serum cross-neutralization capacity against SARS-CoV-2 Delta variant in convalescent COVID-19 patients.

The magnitude and breadth of the neutralizing antibody response against variants of concern following natural infection would provide valuable insights regarding the immune response induced by severe acute respiratory syndrome-related coronavirus(SARS-CoV-2) infection. Herein, 25 patients were followed at 30 ±7 (Visit 1), 90± 15 (Visit 2), and 180 ± 15 (Visit 3) days post symptom onset (PSO). The neutralization titers against both Wuhan-Hu-1 (WT) and Delta variant were analyzed in parallel along with anti-Spike antibodies (anti-S1/S2 immunoglobulin G [IgG]). The median values of half-maximal neutralization titer (NT50 ) for the WT and Delta variants decreased by 75.8% and 82.2% at Visit 2 and by 85.4% and 81.4% at Visit 3, respectively. At Visit 1, the correlation between the anti-S1/S2 IgG and Nabs titers for the Delta variant was moderate for WT (r = 0.58) and weak for the Delta variant (r = 0.39). However, the correlation coefficient consistently remained above 0.7, with a very strong correlation at Visit 3 for both WT and Delta variants (r = 0.81). The dynamics of anti-S1/S2 IgG antibodies, NT50 , and cross-neutralization index correlated at different time points PSO. Longitudinal analysis of the cross-neutralization capacity of immune sera will inform upon the durability of the immune response against SARS CoV-2 variants.

Sotrovimab: A Review of Its Efficacy against SARS-CoV-2 Variants.

Among the anti-Spike monoclonal antibodies (mAbs), the S-309 derivative sotrovimab was the most successful in having the longest temporal window of clinical use, showing a high degree of resiliency to SARS-CoV-2 evolution interrupted only by the appearance of the BA.2.86* variant of interest (VOI). This success undoubtedly reflects rational selection to target a highly conserved epitope in coronavirus Spike proteins. We review here the efficacy of sotrovimab against different SARS-CoV-2 variants in outpatients and inpatients, discussing both randomized controlled trials and real-world evidence. Although it could not be anticipated at the time of its development and introduction, sotrovimab's use in immunocompromised individuals who harbor large populations of variant viruses created the conditions for its eventual demise, as antibody selection and viral evolution led to its eventual withdrawal due to inefficacy against later variant lineages. Despite this, based on observational and real-world data, some authorities have continued to promote the use of sotrovimab, but the lack of binding to newer variants strongly argues for the futility of continued use. The story of sotrovimab highlights the power of modern biomedical science to generate novel therapeutics while also providing a cautionary tale for the need to devise strategies to minimize the emergence of resistance to antibody-based therapeutics.