Spike IgG Research Articles

Heterologous Booster Dose with CORBEVAX following Primary Vaccination with COVISHIELD Enhances Protection against SARS-CoV-2.

Despite effective vaccination programs, waning immunity in the vaccinated populations and the emergence of variants of concern posed a risk of breakthrough infections. A booster dose was demonstrated to provide substantially increased protection against symptomatic disease and hospitalization. We aimed to evaluate immune memory and the efficacy of reducing the rate of SARS-CoV-2 infection post heterologous booster with CORBEVAX after primary vaccination with two doses of COVISHIELD. SARS-CoV-2 S1/S2 spike IgG and RBD-specific antibody responses were elicited with both booster vaccines, with a greater response in individuals receiving heterologous booster. T and B memory responses were increased with booster dose, whereas B memory needed a longer duration to develop in individuals who received a homologous booster (90 days) in comparison to a heterologous booster (30 days). RBD-specific B memory and antibody-secreting (non-memory) B lymphocytes were enhanced with both boosters; however, the duration of response was longer with the heterologous booster compared to the homologous, indicating greater protection with the heterologous booster. The rate of infection 14 days after administration of the heterologous booster was comparatively lower than that of the homologous booster, with the symptoms being much less or asymptomatic.

Association between γ-Glutamyl Transpeptidase and SARS-CoV-2 Spike Antibody Titers among BNT162b2 Vaccine Recipients.

Increased γ-glutamyl transpeptidase (GGT) levels can deplete plasma glutathione, which in turn impairs immune regulation; however, evidence on GGT levels and post-vaccine immunogenicity is lacking. To examine the association between GGT and SARS-CoV-2 spike IgG antibodies. Participants were 1479 medical staff (aged 21 to 75 years) who received a SARS-CoV-2 antibody test after their second vaccine and whose GGT levels were measured before the vaccine rollout. Elevated and highly elevated GGT levels were defined as 51-80 and ≥81 U/L, respectively. Multivariable linear regression was used to calculate the means of SARS-CoV-2 spike IgG. In a basic model, both elevated and highly elevated GGT levels were associated with significantly lower antibody titers. The ratio of mean (95% CI) was 0.83 (0.72-0.97) and 0.69 (0.57-0.84) for elevated and highly elevated GGT levels, respectively. However, these associations were largely attenuated after additional adjustment for potential confounders. An inverse association between GGT levels and antibody titers was found in women [0.70 (0.51-0.97)], normal-weight adults [0.71 (0.51-0.98)], and non-drinkers [0.73 (0.46-1.14)] but not in men, overweight adults, and alcohol drinkers. Circulating GGT concentrations were associated with the humoral immune response after COVID-19 vaccination, but this relationship could be ascribed to confounders such as sex, BMI, and alcohol drinking rather than GGT per se.

Cohort Profile:The Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 vaccines (ENFORCE)

PurposeThe ENFORCE cohort is a national Danish prospective cohort of adults who received a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine as part of the Danish National SARS-CoV-2 vaccination...

Evolution of anti-SARS-CoV-2 spike protein titers after two-dose of COVID-19 vaccination among people living with HIV

BackgroundA community COVID-19 outbreak caused by the B.1.1.7 SARS-CoV-2 variant occurred in Taiwan in May 2021. High-risk populations such as people living with HIV (PLWH) were recommended to receive two doses of COVID-19 vaccines. While SARS-CoV-2 vaccines have demonstrated promising results in general population, real-world information on the serological responses remains limited among PLWH. MethodsPLWH receiving the first dose of SARS-CoV-2 vaccine from 2020 to 2021 were enrolled. Determinations of anti-SARS-CoV-2 spike IgG titers were performed every one to three months, the third dose of the SARS-CoV-2 vaccine or confirmed SARS-CoV-2 infection. All serum samples were tested for anti-nucleocapsid antibody and those tested positive were excluded from analysis. ResultsA total of 1189 PLWH were enrolled: 829 (69.7%) receiving two doses of the AZD1222 vaccine, 232 (19.5%) of the mRNA-1273 vaccine, and 128 (10.8%) of the BNT162b2 vaccine. At all time-points, PLWH receiving two doses of mRNA vaccines had consistently higher antibody levels than those receiving the AZD1222 vaccine (p <0.001 for all time-point comparisons). Factors associated with failure to achieve an anti-spike IgG titer >141 BAU/mL within 12 weeks, included type 2 diabetes mellitus (DM) (adjusted odds ratio [aOR], 2.24; 95% CI, 1.25–4), a CD4 T cell count <200 cells/mm3 upon receipt of the first dose of vaccination (aOR, 3.43; 95% CI, 1.31–9) and two homologous AZD1222 vaccinations (aOR, 16.85; 95%CI, 10.13–28). For those receiving two doses of mRNA vaccines, factors associated with failure to achieve an anti-spike IgG titer >899 BAU/mL within 12 weeks were a CD4 T cell count <200 cells/mm3 on first-dose vaccination (aOR, 3.95; 95% CI, 1.08–14.42) and dual BNT162b2 vaccination (aOR, 4.21; 95% CI, 2.57–6.89). ConclusionsTwo doses of homologous mRNA vaccination achieved significantly higher serological responses than vaccination with AZD1222 among PLWH. Those with CD4 T cell counts <200 cells/mm3 and DM had consistently lower serological responses.

Interim analysis from a phase 2 randomized trial of EuCorVac-19: a recombinant protein SARS-CoV-2 RBD nanoliposome vaccine

BackgroundNumerous vaccine strategies are being advanced to control SARS-CoV-2, the cause of the COVID-19 pandemic. EuCorVac-19 (ECV19) is a recombinant protein nanoparticle vaccine that displays the SARS-CoV-2 receptor-binding domain (RBD) on immunogenic nanoliposomes.MethodsInitial study of a phase 2 randomized, observer-blind, placebo-controlled trial to assess the immunogenicity, safety, and tolerance of ECV19 was carried out between July and October 2021. Two hundred twenty-nine participants were enrolled at 5 hospital sites in South Korea. Healthy adults aged 19–75 without prior known exposure to COVID-19 were vaccinated intramuscularly on day 0 and day 21. Of the participants who received two vaccine doses according to protocol, 100 received high-dose ECV19 (20 μg RBD), 96 received low-dose ECV19 (10 μg RBD), and 27 received placebo. Local and systemic adverse events were monitored. Serum was assessed on days 0, 21, and 42 for immunogenicity analysis by ELISA and neutralizing antibody response by focus reduction neutralization test (FRNT).ResultsLow-grade injection site tenderness and pain were observed in most participants. Solicited systemic adverse events were less frequent, and mostly involved low-grade fatigue/malaise, myalgia, and headache. No clinical laboratory abnormalities were observed. Adverse events did not increase with the second injection and no serious adverse events were solicited by ECV19. On day 42, Spike IgG geometric mean ELISA titers were 0.8, 211, and 590 Spike binding antibody units (BAU/mL) for placebo, low-dose and high-dose ECV19, respectively (p < 0.001 between groups). Neutralizing antibodies levels of the low-dose and high-dose ECV19 groups had FRNT50 geometric mean values of 129 and 316, respectively. Boosting responses and dose responses were observed. Antibodies against the RBD correlated with antibodies against the Spike and with virus neutralization.ConclusionsECV19 was generally well-tolerated and induced antibodies in a dose-dependent manner that neutralized SARS-CoV-2. The unique liposome display approach of ECV19, which lacks any immunogenic protein components besides the antigen itself, coupled with the lack of increased adverse events during boosting suggest the vaccine platform may be amenable to multiple boosting regimes in the future. Taken together, these findings motivate further investigation of ECV19 in larger scale clinical testing that is underway.Trial registrationThe trial was registered at ClinicalTrials.gov as # NCT04783311.

Early CD4+ T cell responses induced by the BNT162b2 SARS-CoV-2 mRNA vaccine predict immunological memory

Longitudinal studies have revealed large interindividual differences in antibody responses induced by SARS-CoV-2 mRNA vaccines. Thus, we performed a comprehensive analysis of adaptive immune responses induced by three doses of the BNT162b2 SARS-CoV-2 mRNA vaccines. The responses of spike-specific CD4+ T cells, CD8+ T cells and serum IgG, and the serum neutralization capacities induced by the two vaccines declined 6 months later. The 3rd dose increased serum spike IgG and neutralizing capacities against the wild-type and Omicron spikes to higher levels than the 2nd dose, and this was supported by memory B cell responses, which gradually increased after the 2nd dose and were further enhanced by the 3rd dose. The 3rd dose moderately increased the frequencies of spike-specific CD4+ T cells, but the frequencies of spike-specific CD8+ T cells remained unchanged. T cells reactive against the Omicron spike were 1.3-fold fewer than those against the wild-type spike. The early responsiveness of spike-specific CD4+ T, circulating T follicular helper cells and circulating T peripheral helper cells correlated with memory B cell responses to the booster vaccination, and early spike-specific CD4+ T cell responses were also associated with spike-specific CD8+ T cell responses. These findings highlight the importance of evaluating cellular responses to optimize future vaccine strategies.

Immunogenicity evaluation of Gam-COVID-Vac (Sputnik V)

In November 2020, the Armed Forces of the Russian Federation began mass immunisation of the personnel with Gam-COVID-Vac (Sputnik V), the first Russia vaccine against the new coronavirus infection (COVID-19). Thus, it became necessary to assess post-vaccination antibody levels and the duration and intensity of humoral immunity to COVID-19.The aim of the study was to investigate the immunogenicity and efficacy of Gam-COVID-Vac in military medical staff after vaccination.Materials and methods: the authors determined the presence of specific antibodies in the serum of individuals immunised with Gam-COVID-Vac (477 volunteers) and COVID-19 convalescents (73 patients), using virus neutralisation (VN), enzyme-linked immunosorbent assay (ELISA) with reagent kits by several manufacturers, and immunoblotting. The results of the study were evaluated using analysis of variance.Results: VN detected virus neutralising antibodies in 90.7% of vaccinated subjects; ELISA, in 95.4%. Both VN and ELISA showed lower antibody levels in the vaccinated over 50 years of age. ELISA demonstrated a significantly higher concentration of anti-SARS-CoV-2 spike IgG in the Gam-COVID-Vac group than in the COVID-19 convalescent group. The correlation between antibody detection results by VN and ELISA was the strongest when the authors used their experimental reagent kit for quantitative detection of virus neutralising antibodies by competitive ELISA with the recombinant human ACE2 receptor. Having analysed the time course of neutralising antibody titres, the authors noted a significant, more than two-fold decrease in geometric means of the titres three months after administration of the second vaccine component.Conclusions: the subjects vaccinated with Gam-COVID-Vac gain effective humoral immunity to COVID-19. The decrease in titres indicates the need for revaccination in 6 months.

Comparison of the duration of viral RNA shedding and anti-SARS-CoV-2 spike IgG and IgM antibody titers in COVID-19 patients who were vaccinated with inactivated vaccines or not: a retrospective study

BackgroundAt present, the role of inactivated vaccines in viral RNA shedding among Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) breakthrough infections is still unknown.MethodsWe collected data of 147 coronavirus disease 2019 (COVID-19) patients with mild-to-moderate illness who were hospitalized in the Third People’s Hospital of Yangzhou from 7 to 20 August 2021 and analyzed the differences in symptoms and laboratory tests among fully vaccinated (FV), partially vaccinated (PV) and unvaccinated (UV) patients.ResultsThe median duration of viral RNA shedding was shorter in the FV (12 [IQR, 9.5–14] days) and PV (13 [IQR, 9–16.75] days) groups than in the UV group (15 [IQR, 11.75–17.25] days) (adjusted P < 0.001 and adjusted P = 0.23, respectively). The median titers of SARS-CoV-2-specific IgG and IgM were significantly higher in the FV (12.29 S/co [IQR, 2.08–63.59] and 0.3 S/co [IQR, 0.05–2.29], respectively) and PV (0.68 S/co [IQR, 0.14–28.69] and 0.12 S/co [0.03–5.23], respectively) groups than in the UV group (0.06 S/co [IQR, 0.03–0.47] and 0.04 S/co [IQR, 0.02–0.07]) (adjusted P < 0.001 and adjusted P = 0.008, respectively).ConclusionsInactivated vaccines may shorten viral RNA shedding in breakthrough infected patients who have mild-to-moderate illness and may improve the ability of the host to generate specific antibodies to infection.

Systemic and T cell-associated responses to SARS-CoV-2 immunisation in gut inflammation (STAR SIGN study): effects of biologics on vaccination efficacy of the third dose of mRNA vaccines against SARS-CoV-2.

Immunosuppressed patients with inflammatory bowel disease (IBD) experience increased risk of vaccine-preventable diseases such as COVID-19. To assess humoral and cellular immune responses following SARS-CoV-2 booster vaccination in immunosuppressed IBD patients and healthy controls. In this prospective, multicentre, case-control study, 139 IBD patients treated with biologics and 110 healthy controls were recruited. Serum anti-SARS-CoV-2 spike IgG concentrations were measured 2-16 weeks after receiving a third mRNA vaccine dose. The primary outcome was to determine if humoral immune responses towards booster vaccines differ in IBD patients under anti-TNF versus non-anti-TNF therapy and healthy controls. Secondary outcomes were antibody decline, impact of previous infection and SARS-CoV-2-targeted T cell responses. Anti-TNF-treated IBD patients showed reduced anti-spike IgG concentrations (geometric mean 2357.4 BAU/ml [geometric SD 3.3]) when compared to non-anti-TNF-treated patients (5935.7 BAU/ml [3.9]; p< 0.0001) and healthy controls (5481.7 BAU/ml [2.4]; p< 0.0001), respectively. In multivariable modelling, prior infection (geometric mean ratio 2.00 [95% CI 1.34-2.90]) and vaccination with mRNA-1273 (1.53 [1.01-2.27]) increased antibody concentrations, while anti-TNF treatment (0.39 [0.28-0.54]) and prolonged time between vaccination and antibody measurement (0.72 [0.58-0.90]) decreased anti-SARS-CoV-2 spike antibodies. Antibody decline was comparable in IBD patients independent of anti-TNF treatment and antibody concentrations could not predict breakthrough infections. Cellular and humoral immune responses were uncoupled, and more anti-TNF-treated patients than healthy controls developed inadequate T cell responses (15/73 [20.5%] vs 2/100 [2.0%]; p= 0.00031). Anti-TNF-treated IBD patients have impaired humoral and cellular immunogenicity following SARS-CoV-2 booster vaccination. Fourth dose administration may be beneficial for these patients.

Comparison of nucleocapsid and spike antibody ELISAs for determining SARS-CoV-2 seropositivity in Kenyan women and infants.

A multitude of enzyme-linked immunosorbent assays (ELISAs) has been developed to detect severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) antibodies since the coronavirus disease 2019pandemic started in late 2019. Assessing the reliability of these assays in diverse global populations is critical. This study compares the use of the commercially available Platelia Total Ab Assay (Bio-Rad) nucleocapsid ELISA to the widely used Mount Sinai spike IgG ELISA in a Kenyan population seroprevalence study. Using longitudinal plasma specimens collected from a mother-infant cohort living in Nairobi, Kenya between May 2019 and December 2020, this study demonstrates that the two assays have a high qualitative agreement (92.7%) and strong correlation of antibody levels (R2 = 0.973) in repeated measures. Within this cohort, seroprevalence detected by either ELISA closely resembled previously published seroprevalence estimates for Kenya during the sampling period and no significant difference in the incidence of SARS-CoV-2 antibody detection by either assay was observed. Assay comparability was not affected by HIV exposure status. These data support the use of the Platelia SARS-CoV-2 Total Ab ELISA as a suitable high-throughput method for seroprevalence studies in Kenya.

The risk factors of SARS-CoV-2 antibody level differences in healthcare workers post vaccination in Siloam hospitals: A nationwide multicenter study

BackgroundSeveral vaccines have been approved against COVID-19, and five have been used in Indonesia. Due to the decrease in antibody levels three to six months after the second dose of CoronaVac, healthcare workers received the third booster of mRNA vaccine (mRNA-1273) to increase the antibody level. This study aimed to evaluate the risk factors of anti-S-RBD IgG levels differences in healthcare workers.MethodsThis study is a retrospective cohort study of 576 healthcare workers without previous SARS-CoV-2 infection who received two doses of CoronaVac and the third dose of mRNA-1273 six months after the second dose. Blood samples were obtained 2nd, 6th, 12th, and 24th weeks after the second dose of CoronaVac vaccine administration, with mRNA-1273 booster on week 20. Quantitative measurements of IgG antibodies were performed with Elecsys Anti-SARS-CoV-2 S immunoassay. We identify the baseline factors predicting post-vaccination antibody titers using univariate and multivariate linear regression analysis.ResultsThis study comprised 576 participants aged 32 years old, 72.05% female, and 45.84% from high-risk occupation subgroups. The median antibodies titer level on the 2nd, 6th, 12th, and 24th weeks after the second vaccine dose administration were 40.99 u/mL, 42.01 u/mL, 54.78 u/mL, and 23,225 u/mL. Antibody levels trended highest in female and younger age group (20-29 years old).ConclusionThe third dose of vaccine increased the quantitative SARS-CoV-2 spike IgG antibody titers and eliminated differences in antibodies titer by gender. Keywords: Antibodies titer, COVID-19, Immune response, S-RBD IgG, Vaccine

Type of mRNA COVID-19 vaccine and immunomodulatory treatment influence humoral immunogenicity in patients with inflammatory rheumatic diseases.

Patients with inflammatory rheumatic diseases (IRD) are at increased risk for worse COVID-19 outcomes. Identifying whether mRNA vaccines differ in immunogenicity and examining the effects of immunomodulatory treatments may support COVID-19 vaccination strategies. We aimed to conduct a long-term, model-based comparison of the humoral immunogenicity following BNT162b2 and mRNA-1273 vaccination in a cohort of IRD patients. Patients from the Swiss IRD cohort (SCQM), who assented to mRNA COVID-19 vaccination were recruited between 3/2021-9/2021. Blood samples at baseline, 4, 12, and 24 weeks post second vaccine dose were tested for anti-SARS-CoV-2 spike IgG (anti-S1). We examined differences in antibody levels depending on the vaccine and treatment at baseline while adjusting for age, disease, and past SARS-CoV-2 infection. 565 IRD patients provided eligible samples. Among monotherapies, rituximab, abatacept, JAKi, and TNFi had the highest odds of reduced anti-S1 responses compared to no medication. Patients on specific combination therapies showed significantly lower antibody responses than those on monotherapy. Irrespective of the disease, treatment, and past SARS-CoV-2 infection, the odds of higher antibody levels at 4, 12, and 24 weeks post second vaccine dose were, respectively, 3.4, 3.8, and 3.8 times higher with mRNA-1273 versus BNT162b2 (p < 0.0001). With every year of age, the odds ratio of higher peak humoral immunogenicity following mRNA-1273 versus BNT162b2 increased by 5% (p < 0.001), indicating a particular benefit for elderly patients. Our results suggest that in IRD patients, two-dose vaccination with mRNA-1273 versus BNT162b2 results in higher anti-S1 levels, even more so in elderly patients.

Importance of the COVID-19 Vaccine Booster Dose in Protection and Immunity.

Background: There is debate on the necessity of booster doses of COVID-19 vaccination, especially in countries with limited resources. Methods: This cross-sectional study was conducted in a referral laboratory in Tehran, Iran. The level of COVID-19 antibodies was measured and compared between individuals regarding the number of COVID-19 vaccine shots. Results: In this study, 176 individuals with a mean age of 36.3 (±11.7) years participated. A total of 112 individuals received two doses of the COVID-19 vaccine, and 64 individuals received three doses. Level of all antibodies was higher in those who received three doses than in those who received two doses of the COVID-19 vaccine. Considering the SARS-CoV-2 Spike IgG, the difference was not statistically significant but for the SARS-CoV-2 RBD IgG and SARS-CoV-2 NAB the difference was statistically significant. Regarding to the background variables, receiving influenza vaccine in the past year, history of autoimmune diseases and past medical history of chicken pox showed a significant association with the number of vaccine doses received. Their effects on the outcome variables assessed with multivariate logistic regression analysis. Conclusion: The results of our study show that a booster dose of the COVID-19 vaccine enhances the antibody response.

Safety and Immunogenicity of a Heterologous Booster of Protein Subunit Vaccine MVC-COV1901 after Two Doses of Adenoviral Vector Vaccine AZD1222.

We report the safety and immunogenicity results in participants administrated with a booster dose of protein subunit vaccine MVC-COV1901 at 12 (Group A) or 24 (Group B) weeks after two doses of AZD1222 (ChAdOx1 nCoV-19). The administration of the MVC-COV1901 vaccine as a booster dose in both groups was generally safe. There were no serious adverse events related to the intervention as adverse events reported were “mild” or “moderate” in nature. In subjects fully vaccinated with two doses of AZD1222, waning antibody immunity was apparent within six months of the second dose of AZD1222. At one month after the MVC-COV1901 booster dose, those who were vaccinated within 12 weeks after the last AZD1222 dose (Group A) had anti-SARS-CoV-2 spike IgG antibody titers and neutralizing antibody titers which were 14- and 6.5-fold increased, respectively, when compared to the titer levels on the day of the booster dose. On the other hand, fold-increase a month post-booster in people who had a booster 24 weeks after the last AZD1222 dose (Group B) were 19.5 and 14.0 times for anti-SARS-CoV-2 spike IgG antibody titers and neutralizing antibody titers, respectively. Among those who were vaccinated within 12 weeks after the last AZD1222 dose, we also observed 5.2- and 5.6-fold increases in neutralizing titer levels against ancestral strain and Omicron variant pseudovirus after the booster dose, respectively. These results support the use of MVC-COV1901 as a heterologous booster for individuals vaccinated with AZD1222. Furthermore, regardless of the dosing schedule, the combination of AZD1222 primary series and MVC-COV1901 booster can be cost-effective and suitably applied to low- and middle-income countries (LMIC).

SARS-CoV-2 spike IgG titres up to 137 days following Comirnaty mRNA COVID-19 vaccination, Israel, February to May 2021.

BackgroundData regarding the long-term protection afforded by vaccination for the SARS-CoV-2 infection are essential for allocation of scarce vaccination resources worldwide.MethodsWe conducted a retrospective cohort study aimed at studying the kinetics of IgG antibodies against SARS-CoV-2 in COVID-19-naïve patients fully vaccinated with two doses of Comirnaty mRNA COVID-19 vaccine. Geometric mean concentrations (GMCs) of antibody levels were reported. Linear models were used to assess antibody levels after full vaccination and their decline over time.ResultsThe study included 4,740 patients and 5,719 serological tests. Unadjusted GMCs peaked 28–41 days after the first dose at 10,174 AU/mL (95% CI: 9,211–11,237) and gradually decreased but remained well above the positivity cut-off. After adjusting for baseline characteristics and repeated measurements, the antibodies half-life time was 34.1 days (95% CI: 33.1–35.2), and females aged 16–39 years with no comorbidities had antibody levels of 20,613 AU/mL (95% CI: 18,526–22,934) on day 28 post-first-dose. Antibody levels were lower among males (0.736 of the level measured in females; 95% CI: 0.672–0.806), people aged 40–59 (0.729; 95% CI: 0.649–0.818) and ≥ 60 years (0.452; 95% CI: 0.398–0.513), and patients having haematological (0.241; 95% CI: 0.190–0.306) or solid malignancies (0.757; 95% CI: 0.650–0.881), chronic kidney disease with glomerular filtration rate (GFR) ≥ 30 (0.434; 95% CI: 0.354–0.532) or with GFR < 30 mL/min (0.176; 95% CI: 0.109–0.287), and immunosuppression (0.273; 95% CI: 0.235–0.317). Body mass index, cardiovascular disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes and inflammatory bowel diseases were not associated with antibody levels.ConclusionsVaccination with two doses resulted in persistently high levels of antibodies (≥ cut-off of 50 AU/mL) up to 137 days post-first-dose. Risk factors for lower antibody levels were identified.

The Performances of Three Commercially Available Assays for the Detection of SARS-CoV-2 Antibodies at Different Time Points Following SARS-CoV-2 Infection.

The aim of this study was to evaluate the performances of three commercially available antibody assays for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies at different time points following SARS-CoV-2 infection. Sera from 536 cases, including 207 SARS-CoV-2 PCR positive, were tested for SARS-CoV-2 antibodies with the Wantai receptor binding domain (RBD) total antibody assay, Liaison S1/S2 IgG assay and Alinity i nucleocapsid IgG assay and compared to a two-step reference ELISA (SARS-CoV-2 RBD IgG and SARS-CoV-2 spike IgG). Diagnostic sensitivity, specificity, predictive values and Cohen’s kappa were calculated for the commercial assays. The assay’s sensitivities varied greatly, from 68.7% to 95.3%, but the specificities remained high (96.9–99.1%). The three tests showed good performances in sera sampled 31 to 60 days after PCR positivity compared to the reference ELISA. The total antibody test performed better than the IgG tests the first 30 days and the nucleocapsid IgG test showed reduced sensitivity two months or more after PCR positivity. Hence, the test performances at different time points should be taken into consideration in clinical practice and epidemiological studies. Spike or RBD IgG tests are preferable in sera sampled more than two months following SARS-CoV-2 infection.

Neutralizing SARS-CoV-2 Spike Antibodies against Omicron in Paired Samples after Two or Three Doses of mRNA Vaccine.

ABSTRACTSARS-CoV-2 antibody levels wane following two-doses of mRNA vaccination. An mRNA booster dose provides increased protection against hospitalization and death. We demonstrated that a booster dose provides a significant increase in the neutralization of the Beta, Delta and Omicron variants in addition to an increased neutralization of the vaccine strain. The total spike IgG measurements, obtained by using commercial kits that target the spike protein from the vaccine strain, may not reflect serum neutralization against variants of concern.IMPORTANCE This study found little to no neutralizing capability following a 2-dose mRNA vaccine series against the omicron variant, and neutralizing capacity to any variant strain tested was lost by 8-months post 2-dose series. However, the mRNA booster dose eliminated the immune escape observed by the Omicron variant, following the 2-dose series. Even more, the neutralizing titers were significantly higher for all variants post-boost, compared to the titers from the post-two-dose series. Our data are unique, using paired samples that eliminate potential confounders that may impact vaccine response. Notably, as seen after the primary two-dose vaccine series, total antibody levels did not correlate perfectly with variant neutralization activity, suggesting that simply testing titers as a measure of protection may not be a long-term solution. Therefore, it is important to reassess the utility of SARS-CoV-2 antibody testing, as current vaccine strain-based testing may not reliably detect reactive antibodies to Omicron or other variants of concern.

Humoral immunity induced by mRNA COVID-19 vaccines in Nursing Home Residents previously infected with SARS-CoV-2

BackgroundNursing home (NH) residents suffered the greatest impact of the COVID-19 pandemic. Limited data are available on vaccine-induced immunity and on the protection ensured by a prior infection in this population.AimsThe present study aims to monitor antibody levels and their persistence over a 6-month period in NH residents according to the history of prior SARS-CoV-2 infection.MethodsWe measured anti-trimeric Spike IgG antibody levels in a sample of 395 residents from 25 NHs in 6 Italian Regions at study enrolment (prior to the first dose of vaccine, T0) and then after 2 (T1) and 6 months (T2) following the first vaccine dose. All participants received mRNA vaccines (BNT162b2 or mRNA-1273). Analyses were performed using log-transformed values of antibody concentrations and geometric means (GM) were calculated.ResultsSuperior humoral immunity was induced in NH residents with previous SARS-CoV-2 infection. (T0: GM 186.6 vs. 6.1 BAU/ml, p < 0.001; T1: GM 5264.1 vs. 944.4 BAU/ml, p < 0.001; T2: GM 1473.6 vs. 128.7 BAU/ml, p < 0.001). Residents with prior SARS-CoV-2 infection receiving two vaccine doses presented significantly higher antibody concentration at T1 and T2. A longer interval between previous infection and vaccination was associated with a better antibody response over time.DiscussionIn a frail sample of NH residents, prior SARS-CoV-2 infection was associated with a higher humoral response to vaccination. Number of vaccine doses and the interval between infection and vaccination are relevant parameters in determining humoral immunity.ConclusionsThese findings provide important information to plan future immunization policies and disease prevention strategies in a highly vulnerable population.

Longitudinal Evaluation of Antibody Persistence in Mother-Infant Dyads After Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Pregnancy.

BackgroundThere are limited data on how COVID-19 severity, timing of infection, and subsequent vaccination impact transplacental transfer and persistence of maternal and infant antibodies.MethodsIn a longitudinal cohort of pregnant women with PCR-confirmed SARS-CoV-2 infection, maternal/infant sera were collected at enrollment, delivery/birth, and 6 months. Anti-SARS-CoV-2 spike IgG, IgM and IgA were measured by ELISA.Results256 pregnant women and 135 infants were enrolled; 148 maternal and 122 neonatal specimens were collected at delivery/birth; 45 maternal and 48 infant specimens were collected at 6 months. Sixty-eight percent of women produced all anti-SARS-CoV-2 isotypes at delivery (IgG, IgM, IgA); 96% had at least one isotype. Symptomatic disease, and vaccination prior to delivery, were associated with higher maternal IgG at L&D. Detectable IgG in infants dropped from 78% at birth to 52% at 6 months. In the multivariate analysis evaluating factors associated with detectable IgG in infants at delivery, significant predictors were 3rd trimester infection (OR 4.0), mild/moderate disease (OR 4.8), severe/critical disease (OR 6.3), and maternal vaccination prior to delivery (OR 18.8). No factors were significant in the multivariate analysis at 6 months postpartum.ConclusionsVaccination in pregnancy post-COVID-19 recovery is a strategy for boosting antibodies in mother-infant dyads.

A Quantitative ELISA to Detect Anti-SARS-CoV-2 Spike IgG Antibodies in Infected Patients and Vaccinated Individuals.

There is an ongoing need for high-precision serological assays for the quantitation of anti-SARS-CoV-2 antibodies. Here, a trimeric SARS-CoV-2 spike (S) protein was used to develop an ELISA to quantify specific IgG antibodies present in serum, plasma, and dried blood spots (DBS) collected from infected patients or vaccine recipients. The quantitative S-ELISA was calibrated with international anti-SARS-CoV-2 immunoglobulin standards to provide test results in binding antibody units per mL (BAU/mL). The assay showed excellent linearity, precision, and accuracy. A sensitivity of 100% was shown for samples collected from 54 patients with confirmed SARS-CoV-2 infection more than 14 days after symptom onset or disease confirmation by RT-PCR and 58 vaccine recipients more than 14 days after vaccination. The assay specificity was 98.3%. Furthermore, antibody responses were measured in follow-up samples from vaccine recipients and infected patients. Most mRNA vaccine recipients had a similar response, with antibody generation starting 2–3 weeks after the first vaccination and maintaining positive for at least six months after a second vaccination. For most infected patients, the antibody titers increased during the second week after PCR confirmation. This S-ELISA can be used to quantify the seroprevalence of SARS-CoV-2 in the population exposed to the virus or vaccinated.