Long-term Humoral Immune Responses Research Articles

Effect of Corticosteroids on Long-Term Humoral and Memory T-Cell Responses in Follow-Up Visit of Hospitalized Patients With COVID-19

Corticosteroids have beneficial effects in improving outcomes in hospitalized patients with severe COVID-19 by suppressing excessive immune responses. However, the effect of corticosteroids on the humoral and T-cell responses of survivors of COVID-19 1 year after infection remains uncertain, as it relates to the extent of immediate, antigen-specific defense provided by protective memory. What is the effect of corticosteroids on long-term humoral and T-cell immune responses? In this retrospective cohort study conducted at a single center, we analyzed data from a cohort who had survived COVID-19 to compare the 1-year seropositivity and titer changes in neutralizing antibodies (NAbs) and SARS-CoV-2-specific antibodies. Additionally, we evaluated the magnitude and rate of SARS-CoV-2-specific T-cell response in individuals who received corticosteroids during hospitalization and those who did not. Our findings indicated that corticosteroids do not statistically influence the kinetics or seropositive rate of NAbs against the Wuhan strain of SARS-CoV-2 from 6months to 1 year. However, subgroup analysis revealed a numerical increase of NAbs titers, from 20.0 to 28.2, in categories where long-term (> 15days) and high-dose (> 560mg) corticosteroids were administered. Similarly, corticosteroids showed no significant effect on nucleoprotein and receptor-binding domain IgG at 1 year, except for spike protein IgG (β, 0.08; 95%CI, 0.04-0.12), which demonstrated a delayed decline of titers. Regarding T-cell immunity, corticosteroids did not affect the rate or magnitude of T-cell responses significantly. However, functional assessment of memory Tcells revealed higher interferon-γ responses in CD4 (β, 0.61; 95%CI, 0.10-1.12) and CD8 (β, 0.63; 95%CI, 0.11-1.15) memory Tcells in the corticosteroids group at 1 year. Based on our findings, short-term and low-dose corticosteroid therapy during hospitalization does not appear to have a significant effect on long-term humoral kinetics or the magnitude and rate of memory T-cell responses to SARS-CoV-2 antigens. However, the potential harmful effects of long-term and high-dose corticosteroid use on memory immune responses require further investigation.

Recombinant BCG vaccine expressing multistage antigens of Mycobacterium tuberculosis provides long-term immunity against tuberculosis in BALB/c mice

ABSTRACT Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) persistently kills nearly 1.5 million lives per year in the world, whereas the only licensed TB vaccine BCG exhibits unsatisfactory efficacy in adults. Taking BCG as a vehicle to express Mtb antigens is a promising way to enhance its efficacy against Mtb infection. In this study, the immune efficacy of recombination BCG (rBCG-ECD003) expressing specific antigens ESAT-6, CFP-10, and nDnaK was evaluated at different time points after immunizing BALB/c mice. The results revealed that rBCG-ECD003 induced multiple Th1 cytokine secretion including IFN-γ, TNF-α, IL-2, and IL-12 when compared to the parental BCG. Under the action of PPD or ECD003, rBCG-ECD003 immunization resulted in a significant increase in the proportion of IL-2+ and IFN-γ+IL-2+ CD4+T cells. Importantly, rBCG-ECD003 induced a stronger long-term humoral immune response without compromising the safety of the parental BCG vaccine. By means of the protective efficacy assay in vitro, rBCG-ECD003 showed a greater capacity to inhibit Mtb growth in the long term. Collectively, these features of rBCG-ECD003 indicate long-term protection and the promising effect of controlling Mtb infection.

2623. Persistence of SARS-CoV-2 S IgG Antibodies in Children that suffered from COVID-19 and Association of Antibody Levels with Vaccination Status

Abstract Background Serum levels of IgG antibodies against SARS-CoV-2 spike protein (S) in children who suffered COVID-19 have been found to last between 4 to 12 months. We aimed to characterize the antibody response against SARS-CoV-2 after 1 year of COVID-19 in unvaccinated and vaccinated children. Methods A cohort study included unvaccinated and vaccinated children (< 18 years) with a previous SARS-CoV-2 infection. Blood samples were collected during the acute phase, in convalescence and 1 year after suffering the disease. For comparative purposes, vaccinated adult relatives who suffered COVID-19 in the same period were included. SARS-CoV-2 S IgG serum levels were determined by immunoassay. Neutralizing activity was determined by the decrease of GFP expression in SARS-CoV-2 S-pseudotyped lentivirus infected HEK-293T cells. Results Eighty-four children were included, median age 8 years (IQR 2-12), 54% (n=45) were females; 38% (n=32) were vaccinated. Also, 50 adults were studied, median age 35 years (IQR 29-44), 76% (n=38) were females. SARS-CoV-2 S IgG levels 1 year after COVID-19 decreased 2.2- to 10.8- fold compared to convalescent levels in unvaccinated children. SARS-CoV-2 S IgG titers positively correlated with neutralizing antibody titers in convalescence and 1 year after COVID-19 (p< 0.05). SARS-CoV-2 S IgG levels were significantly higher in children with incomplete (p=0.0088) and complete/booster (p< 0.0001) vaccination as compared to unvaccinated children. Children that received mRNA vaccines showed higher SARS-CoV-2 IgG titers than children that received an inactivated vaccine (p< 0.0001). SARS-CoV-2 S IgG titers positively correlated with age in vaccinated children (rS=0.4303, p=0.014). SARS-CoV-2 IgG titers 1 year after COVID-19 did not associate with disease severity or the presence of comorbidities. No significant differences in SARS-CoV-2 S IgG levels were found between vaccinated children and adults, at the same vaccination level. Conclusion These findings highlight the importance of child vaccination to maintain a long-term humoral immune response against SARS-CoV-2 despite having been infected. Also, mRNA vaccines elicited a higher antibody response than inactivated vaccines against SARS-CoV-2 in children. Disclosures All Authors: No reported disclosures

Five doses of the mRNA vaccination potentially suppress ancestral-strain stimulated SARS-CoV2-specific cellular immunity: a cohort study from the Fukushima vaccination community survey, Japan.

The bivalent mRNA vaccine is recommended to address coronavirus disease variants, with additional doses suggested for high-risk groups. However, the effectiveness, optimal frequency, and number of doses remain uncertain. In this study, we examined the long-term cellular and humoral immune responses following the fifth administration of the mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients undergoing hemodialysis. To our knowledge, this is the first study to monitor long-term data on humoral and cellular immunity dynamics in high-risk populations after five doses of mRNA vaccination, including the bivalent mRNA vaccine. Whereas most patients maintained humoral immunity throughout the observation period, we observed reduced cellular immune reactivity as measured by the ancestral-strain-stimulated ELISpot assay in a subset of patients. Half of the individuals (50%; 14/28) maintained cellular immunity three months after the fifth dose, despite acquiring humoral immunity. The absence of a relationship between positive controls and T-Spot reactivity suggests that these immune alterations were specific to SARS-CoV-2. In multivariable analysis, participants aged ≥70 years showed a marginally significant lower likelihood of having reactive results. Notably, among the 14 individuals who received heterologous vaccines, 13 successfully acquired cellular immunity, supporting the effectiveness of this administration strategy. These findings provide valuable insights for future vaccination strategies in vulnerable populations. However, further research is needed to evaluate the involvement of immune tolerance and exhaustion through repeated vaccination to optimize immunization strategies.

Immunogenicity and safety of COVID-19 BNT162b2 booster vaccine in end-stage kidney disease patients receiving haemodialysis in Yogyakarta, Indonesia: a cohort prospective study

BackgroundA significant decrease in antibody titres several months after COVID-19 primary vaccination in end-stage kidney disease (ESKD) patients receiving maintenance haemodialysis has recently been reported. The waning in antibody titres has led to the recommendations for a booster dose to increase the antibody titres after vaccination. Consequently, it is crucial to analyse the long-term humoral immune responses after COVID-19 primary vaccination and assess the immunogenicity and safety of booster doses in haemodialysis (HD) patients.MethodsPatients on maintenance haemodialysis who received the primary vaccine of CoronaVac (Sinovac) vaccine were administered with BNT162b2 (Pfizer-BioNTech) as the booster dose. The immunogenicity was assessed before (V1), one month (V2) and eight months (V3) after the primary vaccination, as well as one month after the booster dose (V4). Patients were followed up one month after the booster dose to assess the adverse events (AEs).ResultsThe geometric mean titre (GMT) of anti-SARS-CoV-2 S-RBD IgG antibody at 8 months after the primary vaccination increased significantly to 5,296.63 (95%CI: 2,930.89–9,571.94) U/mL (p = < 0.0001) compared to before the primary vaccination. The GMT also increased significantly to 19,142.56 (95% CI: 13,489.63–27,227.01) U/mL (p < 0.0001) 1 month after the booster vaccine. Meanwhile, the median inhibition rate of neutralizing antibodies (NAbs) at 8 months after the primary vaccine and 1 month after the booster dose were not significantly different (p > 0.9999). The most common AEs after the booster dose included mild pain at the injection site (55.26%), mild fatigue (10.53%), and swelling at the injection site (10.53%). No serious AEs were reported.ConclusionsThe majority of ESKD patients on haemodialysis mounted a good antibody response to the BNT162b2 booster vaccination with tolerable adverse events.

Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity

BackgroundPatients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs.MethodsIMID patients on active treatment with ISPs and controls (i.e. IMID patients not on ISP and healthy controls) with a confirmed SARS-CoV-2 infection before first vaccination were included from an ongoing prospective cohort study (T2B! study). Clinical data on infections and increased disease activity were registered using electronic surveys and health records. A serum sample was collected before first vaccination to measure SARS-CoV-2 anti-receptor-binding domain (RBD) antibodies.ResultsIn total, 193 IMID patients on ISP and 113 controls were included. Serum samples from 185 participants were available, with a median time of 173 days between infection and sample collection. The rate of seropositive IMID patients on ISPs was 78% compared to 100% in controls (p < 0.001). Seropositivity rates were lowest in patients on anti-CD20 (40.0%) and anti-tumor necrosis factor (TNF) agents (60.5%), as compared to other ISPs (p < 0.001 and p < 0.001, respectively). Increased disease activity after infection was reported by 68 of 260 patients (26.2%; 95% CI 21.2–31.8%), leading to ISP intensification in 6 out of these 68 patients (8.8%).ConclusionIMID patients using ISPs showed reduced long-term humoral immune responses after primary SARS-CoV-2 infection, which was mainly attributed to treatment with anti-CD20 and anti-TNF agents. Increased disease activity after SARS-CoV-2 infection was reported commonly, but was mostly mild.Trial registrationNL74974.018.20, Trial ID: NL8900. Registered on 9 September 2020.

Humoral and cellular immune responses after three or four doses of BNT162b2 in patients with hematological malignancies.

Initial responses to coronavirus disease 2019 vaccination are impaired in patients with hematological malignancies. We investigated immune responses after three or four doses of BNT162b2 in patients with myeloid and lymphoid malignancies compared to controls, and identified risk factors for humoral and cellular nonresponse 1 year after first vaccination. In 407 hematological patients (45 myeloid, 362 lymphoid) and 98 matched controls, we measured immunoglobulin G (IgG) and neutralizing antibodies specific for the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at baseline, 3 weeks, 2, 6, and 12 months, and interferon-γ release at 12 months. In patients with lymphoid malignancies, SARS-CoV-2 receptor-binding domain IgG concentration and mean neutralizing capacity was lower than in controls at all time points. A diagnosis of chronic lymphocytic B-cell leukemia (CLL) or lymphoma was associated with humoral nonresponse at 12 months compared to having multiple myeloma/amyloidosis (p < .001 and p = .013). Compared to controls, patients with lymphoid malignancies had increased risk of cellular nonresponse. A lymphoma diagnosis was associated with lower risk of cellular nonresponse compared to patients with multiple myeloma/amyloidosis, while patients with CLL had comparable response rates to patients with multiple myeloma/amyloidosis (p = .037 and p = .280). In conclusion, long-term humoral and cellular immune responses to BNT162b2 were impaired in patients with lymphoid malignancies.

Antibody response dynamics to CoronaVac vaccine and booster immunization in adults and the elderly: A long-term, longitudinal prospective study

The long-term humoral immune response after vaccination varies between vaccines and is dependent on the accuracy of the antibody test. A better understanding of the vaccine immune response may help to define vaccination strategies against coronavirus disease 2019 (COVID-19). To investigate the long-term immunological response to CoronaVac vaccine and determinants of breakthrough COVID-19 infection. A long-term, prospective cohort study involving vaccinated adult and elderly subjects was conducted to investigate the presence of anti-RBD-specific immunoglobulin (Ig)G, anti-nucleocapsid IgG and anti-spike trimeric protein IgG. Antibody level dynamics and risk factors associated with breakthrough COVID-19 infection were investigated. In total, 3902 participants were included in this study. Vaccination with two doses of CoronaVac and a booster dose increased the levels of anti-RBD-specific IgG, anti-nucleocapsid IgG and anti-spike trimeric IgG significantly. In adults, anti-nucleocapsid IgG and anti-spike trimeric IgG levels decreased significantly 7 months after the second dose. In adults and the elderly, the levels of anti-spike trimeric IgG and anti-RBD IgG decreased significantly 4 and 6 months after the booster dose, respectively. Previous exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and anti-spike trimeric IgG titres was independently associated with a lower probability of post-vaccination infection. A significant increase in antibody levels was found after two doses of CoronaVac and a booster dose. Antibody titres declined significantly 7 months post-vaccination in participants who did not receive a booster dose. Higher levels of antibodies and previous SARS-CoV-2 infection were associated with protection against breakthrough COVID-19.

Short- and Long-Term Humoral and Cellular Immune Responses to SARS-CoV-2 Vaccination in Patients with Multiple Sclerosis Treated with Disease-Modifying Therapies.

This study aimed to evaluate short- and long-term humoral and T-cell-specific immune responses to SARS-CoV-2 vaccines in patients with multiple sclerosis (MS) treated with different disease-modifying therapies (DMTs). Single-center observational longitudinal study including 102 patients with MS who consecutively received vaccination against SARS-CoV-2. Serum samples were collected at baseline and after receiving the second dose of the vaccine. Specific Th1 responses following in vitro stimulation with spike and nucleocapsid peptides were analyzed by quantifying levels of IFN-γ. Serum IgG-type antibodies against the spike region of SARS-CoV-2 were studied by chemiluminescent microparticle immunoassay. Patients undergoing fingolimod and anti-CD20 therapies had a markedly lower humoral response than those treated with other DMTs and untreated patients. Robust antigen-specific T-cell responses were detected in all patients except those treated with fingolimod, who had lower IFN-γ levels than those treated with other DMTs (25.8 pg/mL vs. 868.7 pg/mL, p = 0.011). At mid-term follow-up, a decrease in vaccine-induced anti-SARS-CoV-2 IgG antibodies was observed in all subgroups of patients receiving DMTs, although most patients receiving induction DMTs or natalizumab and non-treated patients remained protected. Cellular immunity was maintained above protective levels in all DMT subgroups except the fingolimod subgroup. SARS-CoV-2 vaccines induce robust and long-lasting humoral and cell-mediated specific immune responses in most patients with MS.

In-depth characterization of long-term humoral and cellular immune responses to COVID-19m-RNA vaccination in multiple sclerosis patients treated with teriflunomide or alemtuzumab

The impact of disease-modifying therapies on the efficacy to mount appropriate immune responses to COVID-19 vaccination in patients with multiple sclerosis (MS) is currently under investigation. To characterize long-term humoral and cellular immunity in mRNA-COVID-19 MS vaccinees treated with teriflunomide or alemtuzumab. We prospectively measured SARS-COV-2 IgG, memory B-cells specific for SARS-CoV-2 RBD, and memory T-cells secreting IFN-γ and/or IL-2, in MS patients vaccinated with BNT162b2-COVID-19 vaccine before, 1, 3 and 6 months after the second vaccine dose, and 3-6 months following vaccine booster. Patients were either untreated (N=31, 21 females), under treatment with teriflunomide (N=30, 23 females, median treatment duration 3.7 years, range 1.5-7.0 years), or under treatment with alemtuzumab (N=12, 9 females, median time from last dosing 15.9 months, range 1.8-28.7 months). None of the patients had clinical SARS-CoV-2 or immune evidence for prior infection. Spike IgG titers were similar between untreated, teriflunomide and alemtuzumab treated MS patients both at 1 month (median 1320.7, 25-75 IQR 850.9-3152.8vs. median 901.7, 25-75 IQR 618.5-1495.8, vs. median 1291.9, 25-75 IQR 590.8-2950.9, BAU/ml, respectively), at 3 months (median 1388.8, 25-75 1064.6-2347.6vs. median 1164.3 25-75 IQR 726.4-1399.6, vs. median 837.2, 25-75 IQR 739.4-1868.5 BAU/ml, respectively), and at 6 months (median 437.0, 25-75 206.1-1161.3vs. median 494.3, 25-75 IQR 214.6-716.5, vs. median 176.3, 25-75 IQR 72.3-328.8 BAU/ml, respectively) after the second vaccine dose. Specific SARS-CoV-2 memory B cells were detected in 41.9%, 40.0% and 41.7% of subjects at 1 month, in 32.3%, 43.3% and 25% at 3 months, and in 32.3%, 40.0%, 33.3% at 6 months following vaccination in untreated, teriflunomide treated and alemtuzumab treated MS patients, respectively. Specific SARS-CoV-2 memory T cells were found in 48.4%, 46.7% and 41.7 at 1 month, in 41.9%, 56.7% and 41.7% at 3 months, and in 38.7%, 50.0%, and 41.7% at 6 months, of untreated, teriflunomide-treated and alemtuzumab -treated MS patients, respectively. Administration of a third vaccine booster significantly increased both humoral and cellular responses in all patients. MS patients treated with teriflunomide or alemtuzumab achieved effective humoral and cellular immune responses up to 6 months following second COVID-19 vaccination. Immune responses were reinforced following the third vaccine booster.

Clinical outcome of SARS-CoV-2 infections occurring in multiple myeloma patients after vaccination and prophylaxis with tixagevimab/cilgavimab.

Patients with multiple myeloma (MM) frequently reported immune impairment with an increased risk for infection-related mortality. We aimed to evaluate the immune response in MM patients vaccinated for SARS-CoV-2 during active treatment. We enrolled 158 patients affected by active MM or smoldering MM (SMM) and 40 healthy subjects. All subjects received 2 or 3 doses of the BNT162b2 (Pfizer/BioNTech) vaccine, and the anti-spike IgG values were evaluated after every dose. We applied the Propensity Score Matching (PSM) as a consequence of the limited sample size and its heterogeneity to adjust for differences in baseline clinical variables between MM patients who achieved or not a vaccine response after 2 or 3 doses. At 30 days from the second dose, the median antibodies level in MM was 25.2 AU/mL, lower than in SMM and in the control group. The same results were confirmed after the third dose, with lower median anti-spike IgG levels in MM, compared to SMM and control group. Following PSM, lack of response to SARS-CoV-2 complete vaccination plus boost was associated with age more than 70 years old and use of high-dose of steroids. We failed to identify an association between specific treatment types and reduced vaccine response. The use of prophylaxis with tixagevimab/cilgavimab for 40 non-responder patients after 3 doses of vaccine has proven to be an effective and safe approach in reducing the risk of serious illness in the event of a breakthrough SARS-CoV-2 infection, faced with a mild symptomatic course, and in providing protection instead of long-term humoral immune vaccine responses. Following PSM, only the high-risk cytogenetic abnormalities were associated with an increased risk of developing a breakthrough SARS-CoV-2 infection. Monitoring the immune response is fundamental in MM patients that remain highly vulnerable to SARS-CoV-2 despite the vaccine. The use of prophylaxis with tixagevimab/cilgavimab can guarantee better protection from the severe form of the disease.

Аttenuation мarkers of cold-adapted SARS-CoV-2 variants

BACKGROUND: Unprecedented anti-epidemic measures and the widespread use of vaccines against COVID-19 have reduced the rate of hospitalization and mortality from the disease, but have not stopped the SARS-CoV-2 pandemic spread. The development of live vaccines against COVID-19, capable of providing the formation of a long-term humoral and cellular immune response and cross-protection against new SARS-CoV-2 variants of concern, is relevant. Previously at the I.I. Mechnikov Research Institute of Vaccines and Sera SARS-CoV-2 cold-adapted (ca, cold-adapted) variants were obtained. This work is aimed to search for methodological approaches that allow in vitro screening studies to assess the attenuation (att) phenotype of ca SARS-CoV-2 variants.&#x0D; MATERIALS AND METHODS: The SARS-CoV-2 laboratory strain Dubrovka and its variants were cultured in Vero and Calu-3 cells. Quantitation of the virus was carried out by titration in Vero cells and by real-time RT-PCR. The attenuation (att) phenotype of SARS-CoV-2 variants was determined on an animal model of COVID-19 on Syrian hamsters.&#x0D; RESULTS: In experiments on Syrian hamsters, the presence of the att phenotype in the ca variants of the virus was established. Animals infected with virus ca variants had significantly less weight lost, had less viral load in the lungs and brain and less pronounced pathological changes in the lungs compared to infection with the virulent strain. In vitro experiments on Vero and Calu-3 cells revealed probable attenuation markers of the virus ca variants for syrian hamsters: (1) ability to reproduce at low temperature (ca phenotype); (2) inability to reproduce at 39 C (ts phenotype); (3) changes in the species and tissue specificity of the virus.&#x0D; CONCLUSIONS: The developed methodological approaches to the identification of SARS-CoV-2 attenuation markers are a valuable tool for monitoring the stability of the phenotype of candidate vaccine strains.

Maintenance of Antibody Response in Egyptian Healthcare Workers Vaccinated with ChAdOx1 nCoV-19 Vaccine during Delta and Omicron Variants Pandemic: A Prospective Study.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a constantly evolving virus, resulting in an increased burden on the existing COVID-19 vaccines. Healthcare workers (HCWs) are the first line of defense against the coronavirus disease 2019 (COVID-19) pandemic and have been prioritized among the risk categories receiving the COVID-19 vaccine. This work aimed to investigate the maintenance of antibody response of the Oxford–AstraZeneca vaccine (ChAdOx1/nCoV-19). Methods: Anti-spike immunoglobulin G (IgG) was measured at baseline point (immediately prior to vaccination) and 12- and 24-week (w) points following vaccination. Adverse reactions to the vaccine were reported. Participants were followed up for the incidence of COVID-19 during the 12 w interval between vaccination doses for 24 w after the second dose. Results: A total of 255 HCWs participated in the study. Prior to vaccination, 54.1% experienced COVID-19, 88.2% were seropositive after the first dose, while seropositivity reached 95.7% after the second dose. Following the first and second doses, the anti-spike IgG serum level was significantly higher in subjects with past COVID-19 than in others (p < 0.001 and =0.001, respectively). Conclusions: The Oxford–AstraZeneca vaccine is generally safe and provides a highly effective long-term humoral immune response against the Delta and Omicron variants of SARS-CoV-2.

Long-Term Antibody Response against SARS-CoV-2 in Health Care Workers: Effectiveness of Homologous and Heterologous Regimens and Their Relation to Systemic Vaccine-Associated Symptoms.

This prospective study provides data on the long-term humoral immunogenicity of a heterologous off-label vaccine regimen combining the adenoviral-vectored ChAdOx1 nCoV-19 from Astra-Zeneca (ChAd) with the mRNA-1273 vaccine from Moderna (m1273) in comparison with two different homologous mRNA vaccine schedules. Of the 316 COVID-19 naïve adult health care workers (HCW) included to complete a survey on vaccine-associated symptoms (VAS), 197 had received the homologous BNT162b2 mRNA vaccine from Pfizer/BioNTech (BNT/BNT), 76 the homologous m1273/m1273, and 43 the heterologous ChAd/m1273 vaccine regimen. The concentration of antibodies against SARS-CoV-2 spike protein in plasma 5–7 months after the second vaccine dose was higher in the m1273/m1273 and ChAd/m1273 than the BNT/BNT vaccine group. The frequency of systemic VAS after the first vaccine dose was 86% after ChAd compared with 35% and 39% after BNT and m1273, respectively (p < 0.0001), and after the second vaccine dose, the highest (89%) in the m1273/m1273 group (p < 0.001). Individuals with systemic VAS achieved higher levels of antibodies irrespective of vaccine regimen. In conclusion, VAS serve as a strong predictor of long-term humoral immune response, and the heterologous ChAd/m1273 vaccine regimen provides an at least equal long-term humoral immune response compared with the standard vaccine regimens used in Denmark.

Heterologous vaccination of BNT162b2 in Ad26. COV2.S-vaccinated healthcare workers elicits long-term humoral immune response

Background. To date, there are no immunological data for the SARS-CoV-2 heterologous vaccination schedule in the South African (SA) population. Objectives. To assess and compare the immunogenicity and reactogenicity of the Jansen Ad26.COV2.S vaccine with the Pfizer/BioNTechBNT162b2 booster following prime Ad26.COV2.S in 65 SA healthcare workers. Methods. In a prospective, quantitative, cross-sectional trial on individuals &gt;18 years of age vaccinated with a single Ad26.COV2.S dose or single Ad26.COV2.S and a BNT162b2 single-dose/both doses booster, participants filled in a questionnaire on their demographics, type of vaccination, breakthrough infection/s (BTI/s), vaccine reactogenicity, prior SARS-CoV-2 infection and dates of vaccination. Qualitative analysis for presence/absence of anti-S (spike) immunoglobulin G (IgG) was performed using the Euroimmun anti-IgG enzyme-linked immunoassay kit, and anti-S IgG titres were quantitatively assessed using the Abbott IgG Quant II kit. Results. Between 28 October 2021 and 30 November 2021, 65 individuals were enrolled and assigned as either prime Ad26.COV2.S (n=18) or Ad26.COV2.S with a BNT162b2 supplement (n=47) at Charlotte Maxeke Johannesburg Academic Hospital, SA (mean age 45 years (95% confidence interval (CI) 29.5 - 58), 42 women (64.6%) and 23 men (35.4%)). The median IgG titre for the primed Ad26.COV2.S group was 4 272.55 (95% CI 68.40 - 10 351.40) and that for the BNT162b2 supplement group was 7 360.80 (95% CI 4 207.40 - 15 372.60). In the univariate model, the BNT162b2 supplement group showed a significant 1.99 times higher antibody titre factor (95% CI 0.045 - 5.553; p&lt;0.005) than the Ad26.COV2.S group. In both univariate and multivariate models, age, time since prime vaccination, BTI and prior infection failed to show any statistically significant association (p&gt;0.05) with antibody titres in both groups. However, sex (–55.381 (95% CI –76.984 - –13.498; p=0.018) in a multivariate model was found to have a statistically significant association with anti-S IgG titres observed in both groups. Participants who received their first dose of BNT162b2 9 - 10 months after their prime Ad26.COV2.S (n=44) had a higher degree of antibody response than those who received it earlier. Reactogenicity was observed to be manageable, with mild/moderate adverse effects in the study population. Conclusion. A BNT162b2 supplement given in single or two doses as booster in individuals primed with Ad26.COV2.S induced immunological response, with acceptable and manageable reactogenicity. This study provides novel evidence of the highest degree of antibody response in individuals who received a BNT162b2 first dose 9 - 10 months after prime Ad26.COV2.S, implying that a longer time gap between the two vaccines stimulates higher antibody response than a shorter gap, and that this antibody response can persist for as long as 6 months after the last BNT162b2 dose.

Long-Term Antibody Response to SARS-CoV-2 in Children

Almost 2 years into the pandemic and with vaccination of children significantly lagging behind adults, long-term pediatric humoral immune responses to SARS-CoV-2 are understudied. The C19.CHILD Hamburg (COVID-19 Child Health Investigation of Latent Disease) Study is a prospective cohort study designed to identify and follow up children and their household contacts infected in the early 2020 first wave of SARS-CoV-2. We screened 6113 children < 18 years by nasopharyngeal swab-PCR in a low-incidence setting after general lockdown, from May 11 to June 30, 2020. A total of 4657 participants underwent antibody testing. Positive tests were followed up by repeated PCR and serological testing of all household contacts over 6 months. In total, the study identified 67 seropositive children (1.44%); the median time after infection at first presentation was 83 days post-symptom onset (PSO). Follow-up of household contacts showed less than 100% seroprevalence in most families, with higher seroprevalence in families with adult index cases compared to pediatric index cases (OR 1.79, P = 0.047). Most importantly, children showed sustained seroconversion up to 9 months PSO, and serum antibody concentrations persistently surpassed adult levels (ratio serum IgG spike children vs. adults 90 days PSO 1.75, P < 0.001; 180 days 1.38, P = 0.01; 270 days 1.54, P = 0.001). In a low-incidence setting, SARS-CoV-2 infection and humoral immune response present distinct patterns in children including higher antibody levels, and lower seroprevalence in families with pediatric index cases. Children show long-term SARS-CoV-2 antibody responses. These findings are relevant to novel variants with increased disease burden in children, as well as for the planning of age-appropriate vaccination strategies.

Impact of hypertension on long-term humoral and cellular response to SARS-CoV-2 infection.

It was shown that hypertension delays SARS CoV-2 viral clearance and exacerbates airway hyperinflammation in the respiratory tract. However, it is unknown whether hypertension determines the long-term cellular and humoral response to SARS Cov2. Health care workers (HCWs) after an outbreak of SARS Cov-2 infections were analyzed. Infected HCWs were not vaccinated before blood collection. 5-14 months (median 7 months) after detection of SARS CoV-2 infection, blood was taken to analyze humoral response (S1 IgG and SARS CoV-2 neutralizing antibodies) and cellular (T cell responses to SARS-CoV-2 with Lymphocyte Transformation Test). To identify clinical factors that determine the immune response, a multivariate regression analysis was done considering age, BMI, sex, diabetes, hypertension, smoking, COPD, asthma and time between PCR positivity and blood collection as confounding factors. Infected hypertensive HCWs more often needed to be hospitalized than non-hypertensive HCWs, but were less likely to develop anosmia and myalgia. The long-term humoral and cellular immune response was significantly strengthened in hypertensive versus normotensive infected HCWs. Multivariate regression analysis revealed that hypertension was independently associated with the humoral response to SARS CoV-2 infection. Multivariate regression analysis using same confounding factors for the humoral response showed a clear trend for an association with the cellular response to SARS CoV-2 infection as well. In conclusion, SARS CoV-2 infection strengthened immune response to SARS CoV-2 infection in hypertensive HCWs independent of other risk factors.

Kinetics of anti-nucleocapsid IgG response in COVID-19 immunocompetent convalescent patients

The comprehension of a long-term humoral immune response against SARS-CoV-2 can shed light on the treatment and vaccination strategies of COVID-19 disease, improving the knowledge about this virus infection and/or re-infection. We assessed the IgG antibodies against SARS-CoV-2 nucleocapsid (N) protein (anti-SARS-CoV-2 (N) IgG) in 1441 COVID-19 convalescent patients within 15 months longitudinal study from middle-developed country. The main inclusion criteria was positive RT– PCR result on nasopharyngeal swab samples at least one month before antibody testing and absence of any induced or inherited immunodeficiency. 92.7% of convalescent patients’ serum contained anti-SARS-CoV-2 (N) IgG and only 1.3% of patients had a delayed antibody response. In the majority of convalescent patients’ the durability of antibodies lasted more than one year. The kinetics of anti-SARS-CoV-2 (N) IgG took a bell-shaped character—increased first 25–30 weeks, then started to decrease, but were still detectable for more than 15 months. We found that on the one hand anti-SARS-CoV-2 humoral response level correlates with disease severity, on the other, in particular, the level of peak antibodies correlates with age—older patients develop more robust humoral response regardless of sex, disease severity and BMI.

Long-lasting adaptive immune memory specific to SARS-CoV-2 in convalescent coronavirus disease 2019 stable people with HIV.

While the course of natural immunization specific to SARS-CoV-2 has been described among convalescent coronavirus disease 2019 (COVID-19) people without HIV (PWOH), a thorough evaluation of long-term serological and functional T- and B-cell immune memory among people with HIV (PWH) has not been reported. Eleven stable PWH developing mild ( n = 5) and severe ( n = 6) COVID-19 and 39 matched PWOH individuals with mild (MILD) ( n = 20) and severe (SEV) ( n = 19) COVID-19 infection were assessed and compared at 3 and 6 months after infection for SARS-CoV-2-specific serology, polyfunctional cytokine (interferon-γ [IFN-γ], interleukin 2 [IL-2], IFN-γ/IL-2, IL-21) producing T-cell frequencies against four main immunogenic antigens and for circulating SARS-CoV-2-specific immunoglobulin G (IgG)-producing memory B-cell (mBc). In all time points, all SARS-COV-2-specific adaptive immune responses were highly driven by the clinical severity of COVID-19 infection, irrespective of HIV disease. Notably, while a higher proportion of mild PWH showed a higher decay on serological detection between the two time points as compared to PWOH, persistently detectable IgG-producing mBc were still detectable in most patients (4/4 (100%) for SEV PWH, 4/5 (80%) for MILD PWH, 10/13 (76.92%) for SEV PWOH and 15/18 (83.33%) for MILD PWOH). Likewise, SARS-CoV-2-specific IFN-γ-producing T-cell frequencies were detected in both PWH and PWOH, although significantly more pronounced among severe COVID-19 (6/6 (100%) for SEV PWH, 3/5 (60%) for MILD PWH, 18/19 (94.74%) for SEV PWOH and 14/19 (73.68%) for MILD PWOH). PWH develop a comparable short and long-term natural functional cellular and humoral immune response than PWOH convalescent patients, which are highly influenced by the clinical severity of the COVID-19 infection.

Adjuvant-free cellulose nanofiber vaccine induces permanent humoral immune response in mouse

Vaccines have become one of the most effective strategies to deal with various infectious diseases and chronic noninfectious diseases, such as SARS virus, Novel Coronavirus, cancer, etc. However, recent studies have found that the neutralizing antibody titers induced by vaccines would drop to half level or even lower after vaccination. In this study, we designed a novel small-sized positively charged nanofiber-1 (PEI-CNF-1) as a vaccine carrier, which can induce a high long-term humoral immune response by controlled release of antigen. Further studies showed that PEI-CNF-1 could significantly induce the release of immune response factor IL-1β and bone marrow-derived cell (BMDC) maturation. Moreover, compare to other cellulose nanofibers (CNFs), PEI-CNF-1 combined antigen (ovalbumin, OVA) induced and maintained the highest and longest antibody titers after vaccination. Interestingly, the antibody titers have no significant difference between at 21 and 90 d. Mechanically, we found that PEI-NCF-1 not only could control the slow-release of antigen, but also could be more easily swallowed by macrophages and metabolized by the bodies, thus presenting antigen more effectively. In conclusion, we believe that PEI-CNF-1 have a very high application prospect in inducing long-term humoral immune response, so as to achieve efficient prevention effect to epidemic viruses.