Within-host modeling to measure dynamics of antibody responses after natural infection or vaccination: A systematic review.

BACKGROUND: Within-host models describe the dynamics of immune cells when encountering a pathogen, and how these dynamics can lead to an individual-specific immune response. This systematic review aims to summarize which within-host methodology has been used to study and quantify antibody kinetics after infection or vaccination. In particular, we focus on data-driven and theory-driven mechanistic models. MATERIALS: PubMed and Web of Science databases were used to identify eligible papers published until May 2022. Eligible publications included those studying mathematical models that measure antibody kinetics as the primary outcome (ranging from phenomenological to mechanistic models). RESULTS: We identified 78 eligible publications, of which 8 relied on an Ordinary Differential Equations (ODEs)-based modelling approach to describe antibody kinetics after vaccination, and 12 studies used such models in the context of humoral immunity induced by natural infection. Mechanistic modeling studies were summarized in terms of type of study, sample size, measurements collected, antibody half-life, compartments and parameters included, inferential or analytical method, and model selection. CONCLUSIONS: Despite the importance of investigating antibody kinetics and underlying mechanisms of (waning of) the humoral immunity, few publications explicitly account for this in a mathematical model. In particular, most research focuses on phenomenological rather than mechanistic models. The limited information on the age groups or other risk factors that might impact antibody kinetics, as well as a lack of experimental or observational data remain important concerns regarding the interpretation of mathematical modeling results. We reviewed the similarities between the kinetics following vaccination and infection, emphasising that it may be worth translating some features from one setting to another. However, we also stress that some biological mechanisms need to be distinguished. We found that data-driven mechanistic models tend to be more simplistic, and theory-driven approaches lack representative data to validate model results.

Severe acute respiratory syndrome coronavirus-2 antibody response after Moderna vaccine booster on healthcare providers.

INTRODUCTION: As an endeavor to control SARS-CoV-2 infection, the Moderna vaccine booster was given to healthcare workers to prevent reinfection and reduce the risk of complications from COVID-19. A heterologous booster vaccine is also thought to provide better protection against the current SARS-CoV-2 variants of concern. However, research that evaluates the effectiveness of the Moderna vaccine booster and the resulting SARS-CoV-2 antibody concentration is needed. OBJECTIVE: To evaluate the concentration of SARS-CoV-2 antibodies after the Moderna vaccine booster and the severity of SARS-CoV-2 infection before and after the Moderna vaccine booster. RESULTS: A total of 93 healthcare providers who received Moderna vaccine booster were included in the study. Examination of antibody concentration 3 months after the booster showed an average concentration of 10081.65 U/mL. There was an increase in antibody concentration before the booster and 3 months after, from a median of 1.7 U/mL to 9540 U/mL. Every subject showed a statistically significant increment of antibody concentration 3 months after the booster (p < 0.01). Thirty-seven (39.8%) subjects received two doses of the Sinovac vaccine and were confirmed to have COVID-19 with the Delta variant. After the booster, 26 (28%) subjects were infected with the Omicron Variant. Among the subjects who received two doses of the Sinovac vaccine and were confirmed with COVID-19, 36 (30.1%) had mild symptoms, and 1 (1.1%) was asymptomatic. CONCLUSIONS: Heterologous Moderna vaccine booster effectively increases antibody response against SARS-CoV-2 variants and shows mild symptoms of COVID-19 infection.

Predictors of a weak antibody response to COVID-19 mRNA vaccine in systemic lupus erythematosus.

OBJECTIVES: To characterize the antibody response to COVID-19 mRNA vaccination in patients with Systemic Lupus Erythematosus (SLE) and identify predictors of poor response. METHODS: SLE patients who are followed at the Beth Israel Deaconess Medical Center Lupus Cohort (BID-LC) were enrolled. SARS-CoV-2 IgG Spike antibody was measured in patients who received two doses of either the BNT162b2 (Pfizer-BioNTech) or the mRNA-1273 (Moderna) COVID-19 vaccine (n = 62). We defined non-responders as patients with an IgG Spike antibody titer less than two-fold (< 2) the index value of the test and responders as patients with antibody levels greater or equal to two-fold (≥ 2). A web-based survey was used to collect information regarding immunosuppressive medication use and SLE flares after vaccination. RESULTS: In our cohort of lupus patients, 76% were vaccine responders. The use of two or more immunosuppressive drugs was associated with being a non-responder (Odds Ratio 5.26; 95% CI 1.23-22.34, p = 0.02). Both Belimumab use and higher Prednisone dose were associated with vaccine non-response (p = 0.04 and p = 0.04). The non-responder group had higher mean levels of serum IL-18 than the responder group (p = 0.04) as well as lower C3 levels (p = 0.01). Lupus flares and breakthrough infections were uncommon post-vaccination. CONCLUSIONS: Immunosuppressive medications have a negative impact on vaccine humoral response in SLE individuals. We observed a trend towards vaccine no-response in BNT162b2 recipients and a relationship between IL-18 and impaired antibody response that merits further investigation.

Effects of Antibody Response after Booster Vaccination on SARS-CoV-2 Breakthrough Infections and Disease Outcomes in Advanced Cancer Patients: A Prospective Analysis of the Vax-on-Third Study.

(1) Background: The clinical implications of COVID-19 outbreaks following SARS-CoV-2 vaccination in immunocompromised recipients are a worldwide concern. Cancer patients on active treatment remain at an increased risk of developing breakthrough infections because of waning immunity and the emergence of SARS-CoV-2 variants. There is a paucity of data on the effects of COVID-19 outbreaks on long-term survival outcomes in this population. (2) Methods: We enrolled 230 cancer patients who were on active treatment for advanced disease and had received booster dosing of an mRNA-BNT162b2 vaccine as part of the Vax-On-Third trial between September 2021 and October 2021. Four weeks after the third immunization, IgG antibodies against the spike receptor domain of SARS-CoV-2 were tested in all patients. We prospectively evaluated the incidence of breakthrough infections and disease outcomes. The coprimary endpoints were the effects of antibody titers on the development of breakthrough infections and the impact of COVID-19 outbreaks on cancer treatment failure. (3) Results: At a median follow-up of 16.3 months (95% CI 14.5-17.0), 85 (37%) patients developed SARS-CoV-2 infection. Hospitalization was required in 11 patients (12.9%) and only 2 (2.3%) deaths related to COVID-19 outbreaks were observed. Median antibody titers were significantly lower in breakthrough cases than in non-cases (291 BAU/mL (95% CI 210-505) vs. 2798 BAU/mL (95% CI 2323-3613), p < 0.001). A serological titer cut-off below 803 BAU/mL was predictive of breakthrough infection. In multivariate testing, antibody titers and cytotoxic chemotherapy were independently associated with an increased risk of outbreaks. Time-to-treatment failure after booster dosing was significantly shorter in patients who contracted SARS-CoV-2 infection (3.1 months (95% CI 2.3-3.6) vs. 16.2 months (95% CI 14.3-17.0), p < 0.001) and had an antibody level below the cut-off (3.6 months (95% CI 3.0-4.5) vs. 14.6 months (95% CI 11.9-16.3), p < 0.001). A multivariate Cox regression model confirmed that both covariates independently had a worsening effect on time-to-treatment failure. (4) Conclusions: These data support the role of vaccine boosters in preventing the incidence and severity of COVID-19 outbreaks. Enhanced humoral immunity after the third vaccination significantly correlates with protection against breakthrough infections. Strategies aimed at restraining SARS-CoV-2 transmission in advanced cancer patients undergoing active treatment should be prioritized to mitigate the impact on disease outcomes.

Concluding Remarks for the Special Issue on RNA Viruses and Antibody Response.

Infectious diseases represent one of the major public health concerns on the global level [...].

Severe Acute Respiratory Syndrome Coronavirus 2 Infection History and Antibody Response to 3 Coronavirus Disease 2019 Messenger RNA Vaccine Doses.

BACKGROUND: Data on antibody kinetics are limited among individuals previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From a cohort of healthcare personnel and other frontline workers in 6 US states, we assessed antibody waning after messenger RNA (mRNA) dose 2 and response to dose 3 according to SARS-CoV-2 infection history. METHODS: Participants submitted sera every 3 months, after SARS-CoV-2 infection, and after each mRNA vaccine dose. Sera were tested for antibodies and reported as area under the serial dilution curve (AUC). Changes in AUC values over time were compared using a linear mixed model. RESULTS: Analysis included 388 participants who received dose 3 by November 2021. There were 3 comparison groups: vaccine only with no known prior SARS-CoV-2 infection (n = 224); infection prior to dose 1 (n = 123); and infection after dose 2 and before dose 3 (n = 41). The interval from dose 2 and dose 3 was approximately 8 months. After dose 3, antibody levels rose 2.5-fold (95% confidence interval [CI] = 2.2-3.0) in group 2 and 2.9-fold (95% CI = 2.6-3.3) in group 1. Those infected within 90 days before dose 3 (and median 233 days [interquartile range, 213-246] after dose 2) did not increase significantly after dose 3. CONCLUSIONS: A third dose of mRNA vaccine typically elicited a robust humoral immune response among those with primary vaccination regardless of SARS-CoV-2 infection >3 months prior to boosting. Those with infection <3 months prior to boosting did not have a significant increase in antibody concentrations in response to a booster.

Antibody response and safety of inactivated SARS-CoV-2 vaccines in chronic hepatitis B patients with and without cirrhosis.

Background: The immune response and safety of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with chronic hepatitis B (CHB), especially those with cirrhosis, are not clear. Therefore, this study was conducted to evaluate the efficacy and safety of inactivated SARS-CoV-2 vaccines among CHB patients with and without cirrhosis. Patients and methods: A total of 643 CHB patients who received two doses of inactivated SARS-CoV-2 vaccines (BBIBP-CorV and CoronaVac) were enrolled. Serum samples were collected and tested for SARS-CoV-2 S-receptor-binding domain (S-RBD) immunoglobulin G (IgG) at enrollment. Data on adverse events (AEs) within 7 days after the second dose were obtained using a questionnaire. Results: A total of 416 non-cirrhotic and 227 cirrhotic patients were included in the analysis. Cirrhotic patients had lower antibody titers than non-cirrhotic patients after adjusting for age, sex, and time interval (2.45 vs. 2.60 ng/ml, p = 0.034). Furthermore, the study revealed that cirrhotic patients demonstrated a slower rate of seropositivity increase, with the highest rate being recorded at week 4 and reaching 94.7%. On the other hand, among non-cirrhotic patients, the seropositivity rate peak was observed at week 2 and reached 96.0%. In addition, cirrhotic patients displayed a more rapid decline in the seropositivity rate, dropping to 54.5% after ≥16 weeks, while non-cirrhotic patients exhibited a decrease to 67.2% after the same time period. The overall incidence of AEs was low (18.4%), and all AEs were mild and self-limiting. In addition, 16.0% of participants had mild liver function abnormalities, and half of them returned to normality within the next 6 months without additional therapy. The participants who experienced liver function abnormalities showed a higher seropositivity rate and antibody titer than those who did not (91.6% vs. 79.5%, p = 0.005; 2.73 vs. 2.41 ng/ml, p < 0.001). Conclusion: Cirrhotic CHB patients had lower antibody titers to inactivated SARS-CoV-2 vaccines than non-cirrhotic patients. The vaccines were generally well tolerated in both non-cirrhotic and cirrhotic CHB patient groups. Patients with abnormal liver function may have a better antibody response than those without.

[Comparative Analyses of IgA Antibody Response of Non-COVID-19 Infected People Over 60 Years Old Following CoronaVac and Pfizer-BioNTech COVID-19 Vaccination]. / COVID-19 Enfeksiyonu Geçirmeyen 60 Yas Üstü Kisilerde CoronaVac ve Pfizer-BioNTech Asisi Sonrasi IgA Antikor Yaniti Karsilastirilmasi.

The formation rate, magnitude, and duration of the antibody-mediated humoral immune response that develops against different viral proteins of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are considered important in vaccine success. It is known that the response to vaccinations decreases due to immunosenescence in older adults. This study was aimed to investigate the levels of serum IgA response at 1st and 3rd month after vaccination of people over 60 years old who were immunized with CoronaVac and Pfizer-BioNTech. A total of 35 people living in the North Cyprus who have not previously had COVID-19 infection were included in the study. After the 2nd dose of vaccination, serum IgA levels were measured after the 1st and 3rd month with the anti-SARS-CoV-2 IgA (Euroimmun, Lubeck, Germany) kit. The statistical significance was determined as 0.05 in the whole study. SPSS and GraphPad Prism software were used for calculations, analyses and graphs. The possible effect of demographic variables on serum IgA level was compared between the vaccine groups and it was found that there was no statistically significant difference between them. For the IgA titer-positive individuals who had been vaccinated with the Pfizer-BioNTech vaccine, for both 1st and 3rd months were observed to be higher than CoronaVac vaccinated IgA titer-positive individuals. In individuals who received the CoronaVac vaccine, there was a statistically significant change in serum IgA levels between 1st and 3rd months, but there was no statistically significant change in the Pfizer-BioNTech vaccine administered group. When the Pfizer/BioNTech and CoronaVac vaccines were compared with each other in terms of serum IgA antibody titers, it was found that the mean serum IgA levels of the individuals in the Pfizer/BioNTech group were statistically higher at the 1st and 3rd months than the CoronaVac group. Serum IgA titers in both vaccine groups were statistically significantly decreased from 1st month to 3rd month. This study showed that the Pfizer/BioNTech vaccine induced higher SARS-CoV-2 specific serum IgA antibodies than the CoronaVac vaccine and remained seropositive for a longer time in individuals aged 60 years and older. It is believed that the serum IgA levels that were determined may not reflect the serum IgA levels. However, these findings support the studies in other literature, showing that the Pfizer-BioNTech mRNA vaccine induces higher SARS-CoV-2 specific serum IgA antibodies than the inactive CoronaVac vaccine and that it remains seropositive for a longer period of time. This study is important as it is the first study to compare the SARS-CoV-2 IgA antibody responses of individuals over 60 years of age in the Turkish Republic of Northern Cyprus in two different vaccine groups.

Seroprevalence and durability of antibody responses to AstraZeneca vaccination in Ugandans with prior mild or asymptomatic COVID-19: implications for vaccine policy.

Introduction: The duration and timing of immunity conferred by COVID-19 vaccination in sub-Saharan Africa are crucial for guiding pandemic policy interventions, but systematic data for this region is scarce. This study investigated the antibody response after AstraZeneca vaccination in COVID-19 convalescent Ugandans. Methods: We recruited 86 participants with a previous rt-PCR-confirmed mild or asymptomatic COVID-19 infection and measured the prevalence and levels of spike-directed IgG, IgM, and IgA antibodies at baseline, 14 and 28 days after the first dose (priming), 14 days after the second dose (boosting), and at six- and nine-months post-priming. We also measured the prevalence and levels of nucleoprotein-directed antibodies to assess breakthrough infections. Results: Within two weeks of priming, vaccination substantially increased the prevalence and concentrations of spike-directed antibodies (p < 0.0001, Wilcoxon signed rank test), with 97.0% and 66% of vaccinated individuals possessing S-IgG and S-IgA antibodies before administering the booster dose. S-IgM prevalence changed marginally after the initial vaccination and barely after the booster, consistent with an already primed immune system. However, we also observed a rise in nucleoprotein seroprevalence, indicative of breakthroughs six months after the initial vaccination. Discussion: Our results suggest that vaccination of COVID-19 convalescent individuals with the AstraZeneca vaccine induces a robust and differential spike-directed antibody response. The data highlights the value of vaccination as an effective method for inducing immunity in previously infected individuals and the importance of administering two doses to maintain protective immunity. Monitoring anti-spike IgG and IgA when assessing vaccine-induced antibody responses is suggested for this population; assessing S-IgM will underestimate the response. The AstraZeneca vaccine is a valuable tool in the fight against COVID-19. Further research is needed to determine the durability of vaccine-induced immunity and the potential need for booster doses.

The impact of CoronaVac on the neutralization breadth and magnitude of the antibody response to SARS-CoV-2 viruses.

Although immune response enhancement has been reported after primary and booster vaccines of CoronaVac, neutralization breadth of SARS-CoV-2 variants is still unclear. In the present study, we examined the neutralization magnitude and breadth of SARS-CoV-2 variants including Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529) in 33 convalescent COVID-19 patients and a cohort of 55 medical staff receiving primary CoronaVac vaccines and an additional homologous booster dose. Results showed that, as compared with the two-dose primary vaccination, the homologous booster dose achieved 2.24-, 3.98-, 4.58- and 2.90-fold increase in neutralization titer against wild-type, Beta, Delta, and Omicron, respectively. After booster dose, neutralization titer reduction for variants was less than that after the primary vaccine or that for convalescents. The proportion of recipients able to neutralize 2 or more variants increased from 36.36% post the primary vaccination to 87.27% after the booster. Significant increase in neutralization breadth of 1.24 (95% confidence interval (CI), 0.89-1.59) variants was associated with a log10 increase in neutralization titer against the wild-type. In addition, anti-RBD IgG level was identified as an excellent surrogate for positive neutralization of SARS-CoV-2 and neutralization breadth of variants. These findings highlight the value of an additional homologous CoronaVac dose in broadening the cross-neutralization against SARS-CoV-2 variants, and are critical for informing the booster dose vaccination efforts.

Pilot genome-wide association study of antibody response to inactivated SARS-CoV-2 vaccines.

Vaccines are a key weapon against the COVID-19 pandemic caused by SARS-CoV-2. However, there are inter-individual differences in immune response to SARS-CoV-2 vaccines and genetic contributions to these differences have barely been investigated. Here, we performed genome-wide association study (GWAS) of antibody levels in 168 inactivated SARS-CoV-2 vaccine recipients. A total of 177 SNPs, corresponding to 41 independent loci, were identified to be associated with IgG, total antibodies or neutral antibodies. Specifically, the rs4543780, the intronic variant of FAM89A gene, was associated with total antibodies level and was annotated as a potential regulatory variant affecting gene expression of FAM89A, a biomarker differentiating bacterial from viral infections in febrile children. These findings might advance our knowledge of the molecular mechanisms driving immunity to SARS-CoV-2 vaccine.

Booster dose of mRNA vaccine augments waning T cell and antibody responses against SARS-CoV-2.

A gradual decay in humoral and cellular immune responses over time upon SAR1S-CoV-2 vaccination may cause a lack of protective immunity. We conducted a longitudinal analysis of antibodies, T cells, and monocytes in 25 participants vaccinated with mRNA or ChAdOx1-S up to 12 weeks after the 3rd (booster) dose with mRNA vaccine. We observed a substantial increase in antibodies and CD8 T cells specific for the spike protein of SARS-CoV-2 after vaccination. Moreover, vaccination induced activated T cells expressing CD69, CD137 and producing IFN-γ and TNF-α. Virus-specific CD8 T cells showed predominantly memory phenotype. Although the level of antibodies and frequency of virus-specific T cells reduced 4-6 months after the 2nd dose, they were augmented after the 3rd dose followed by a decrease later. Importantly, T cells generated after the 3rd vaccination were also reactive against Omicron variant, indicated by a similar level of IFN-γ production after stimulation with Omicron peptides. Breakthrough infection in participants vaccinated with two doses induced more SARS-CoV-2-specific T cells than the booster vaccination. We found an upregulation of PD-L1 expression on monocytes but no accumulation of myeloid cells with MDSC-like immunosuppressive phenotype after the vaccination. Our results indicate that the 3rd vaccination fosters antibody and T cell immune response independently from vaccine type used for the first two injections. However, such immune response is attenuated over time, suggesting thereby the need for further vaccinations.

Antibody response to the third dose of inactivated COVID-19 vaccine in people living with HIV (PLWH): A longitudinal cohort.

The immunogenicity induced by the third dose of inactivated coronavirus disease 2019 (COVID-19) vaccines in people living with HIV (PLWH) is unclear, and relevant literature is extremely scarce. It is important to add evidence on the humoral immune response induced by the third dose of inactivated COVID-19 vaccine in PLWH. We collected peripheral venous blood for spike receptor binding domain-protein specific immunoglobulin G (S-RBD-IgG) antibody tests at 28 days after the second dose (T1 ), 180 days after the second dose (T2 ) and 35 days after the third dose (T3 ) of inactivated COVID-19 vaccines in PLWH. The differences in S-RBD-IgG antibody levels and specific seroprevalence among T1 , T2 , and T3 time periods were analyzed, and the effects of age, vaccine brand, and CD4+ T cell count on the levels and specific seroprevalence of S-RBD-IgG antibody induced by the third dose in PLWH were examined. The third dose of inactivated COVID-19 vaccines induced strong S-RBD-IgG antibody responses in PLWH. The levels and specific seroprevalence of S-RBD-IgG antibody were significantly higher than those at 28 and 180 days after the second dose and were not affected by vaccine brand or CD4+ T cell count. Younger PLWH produced higher levels of S-RBD-IgG antibody. The third dose of inactivated COVID-19 vaccine showed good immunogenicity in PLWH. It is necessary to popularize the third dose in the PLWH population, especially PLWH who do not respond to two doses of inactivated COVID-19 vaccines. Meanwhile, the durability of the protection provided by the third dose in PLWH must be continuously monitored.

Metabolic Adaptations Correlated with Antibody Response after Immunization with Inactivated SARS-CoV-2 in Brazilian Subjects.

The adsorbed vaccine SARS-CoV-2 (inactivated) produced by Sinovac (SV) was the first vaccine against COVID-19 to be used in Brazil. To understand the metabolic effects of SV in Brazilian subjects, NMR-based metabolomics was used, and the immune response was studied in Brazilian subjects. Forty adults without (group-, n = 23) and with previous COVID-19 infection (group+, n = 17) were followed-up for 90 days postcompletion of the vaccine regimen. After 90 days, our results showed that subjects had increased levels of lipoproteins, lipids, and N-acetylation of glycoproteins (NAG) as well as decreased levels of amino acids, lactate, citrate, and 3-hydroxypropionate. NAG and threonine were the highest correlated metabolites with N and S proteins, and neutralizing Ab levels. This study sheds light on the immunometabolism associated with the use of SV in Brazilian subjects from Rio de Janeiro and identifies potential metabolic markers associated with the immune status.

Antibody response to SARS-CoV-2 WT and Omicron BA.4/5 of inactivated COVID-19 vaccine in patients with lung cancer after second and booster immunization.

COVID-19 inactivated vaccine-induced humoral responses in patients with lung cancer (LCs) to SARS-CoV-2 wild-type (WT) strain and variants BA.4/5 after the primary 2-dose and booster vaccination remained unknown. We conducted a cross-sectional study in 260 LCs, 140 healthy controls (HC) and additional 40 LCs with serial samples by detecting total antibodies, IgG anti-RBD and neutralizing antibodies (NAb) toward WT and BA.4/5. SARS-CoV-2-specific antibody responses were augmented by the booster dose of inactivated vaccines in LCs, whereas they were lower than that in HCs. Enhanced humoral responses waned over time after triple injection, notably in NAb against WT and BA.4/5. The NAb against BA.4/5 was much lower than WT. Age ≥ 65 was risk factor for immunization of NAb to WT. Undergoing treatment resulted in a lower antibody response than those without and radiotherapy was a also risk factor for seroconversion of NAb to WT. Lower lymphocyte counts contributed to a lower titer of IgG anti-RBD and NAb against BA.4/5 in LCs than HCs. Specifically, total B cells, CD4+T cells and CD8+T counts were correlated with the humoral response. These results should be taken into consideration for the elderly patients under treatment.

Evaluation of T and B cell immunophenotyping and antibody response post Covid-19 vaccination.

PURPOSE: To evaluate T and B cell subsets and IgG antibodies in response to SARS-CoV-2 post COVID-19 vaccination. METHODS: A total of 50 healthy adults (18-60 years) receiving anti-SARS-CoV-2 vaccination (COVISHIELD) were recruited for the study. Blood samples were collected from participants at 3 time points; just before vaccination (Visit 0, V0), just before booster dose (Visit 1, V1) and 6th month after 1st dose (Visit 2, V2). Peripheral blood mononuclear cell isolation was done and evaluated for T and B cell subsets by Flow cytometry. Quantitative determination of IgG antibodies to SARS-CoV-2 was done by Chemiluminescence immunoassay in all samples. Final data for all three visits was available for 37 participants who remained healthy. Ethics approval was obtained from Medanta Institution of Ethics Committee vide MICR No. 1290/2021 dated 24th May 2021. RESULTS: Mean age of the participants was 34.6 â€‹± â€‹5.7 years (Range: 24-45 years). Highly significant improvement in SARS-CoV-2 IgG levels was observed after each visit {Mean IgG: (V0 v/s. V1: 133.8 â€‹± â€‹339.2AU/ml v/s. 434.5 â€‹± â€‹519.2AU/ml; p-value â€‹= â€‹0.003) and V0 v/s. V2: 133.8 â€‹± â€‹339.2AU/ml v/s. 420.9 â€‹± â€‹394.2AU/ml; p-value â€‹= â€‹0.002) Between visits 0 and 1, the mean value for CD4 Naïve T cells showed significant increase, while CD4 central memory (CM) T cells showed significant decrease. Between visits 0 and 2 the mean values for CD4 Naïve T cells, CD8 Naïve T cells and Pre germinal centre (Pre GC) B cells showed significant increase. During the same period the mean values for CD4CM, CD8 effector memory (EM) and CD8 CM T cells showed significant decrease. CONCLUSION: It is concluded that both, humoral and cellular immunity, play an important role in maintaining immunity against COVID-19 infection, following COVISHIELD vaccination. Moreover, in subjects with normalisation of antibody levels post vaccination, persistence of T cell subsets may still offer some immunity.

Total recall? Understanding the effect of antigenic distance on original antigenic sin.

Vaccination-induced antibodies are critical for protective immunity against pathogenic threats. "Original antigenic sin" (OAS), also referred to as imprinting, is the observed phenomenon whereby exposure to antigenic stimuli bias future antibody responses. This Commentary describes a recently elegant model published in Nature by Schiepers et al. which allows us to delve deeper into the processes and mechanisms of OAS than ever before.

Antibody response elicited by the SARS-CoV-2 vaccine booster in patients with multiple sclerosis: Who gains from it?

BACKGROUND AND PURPOSE: Although two doses of COVID-19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease-modifying therapies (DMTs) showed less efficient responses. METHODS: This prospective multicenter observational study evaluates differences in immune response after a third vaccine dose in pwMS. RESULTS: Four hundred seventy-three pwMS were analyzed. Compared to untreated patients, there was a 50-fold decrease (95% confidence interval [CI] = 14.3-100.0, p < 0.001) in serum SARS-CoV-2 antibody levels in those on rituximab, a 20-fold decrease (95% CI = 8.3-50.0, p < 0.001) in those on ocrelizumab, and a 2.3-fold decrease (95% CI = 1.2-4.6, p = 0.015) in those on fingolimod. As compared to the antibody levels after the second vaccine dose, patients on the anti-CD20 drugs rituximab and ocrelizumab showed a 2.3-fold lower gain (95% CI = 1.4-3.8, p = 0.001), whereas those on fingolimod showed a 1.7-fold higher gain (95% CI = 1.1-2.7, p = 0.012), compared to patients treated with other DMTs. CONCLUSIONS: All pwMS increased their serum SARS-CoV-2 antibody levels after the third vaccine dose. The mean antibody values of patients treated with ocrelizumab/rituximab remained well below the empirical "protective threshold" for risk of infection identified in the CovaXiMS study (>659 binding antibody units/mL), whereas for patients treated with fingolimod this value was significantly closer to the cutoff.

Immune Response to Seasonal Influenza Vaccination in Multiple Sclerosis Patients Receiving Cladribine.

Cladribine has been approved for the treatment of multiple sclerosis (MS) and its administration results in a long-lasting depletion of lymphocytes. As lymphopenia is known to hamper immune responses to vaccination, we evaluated the immunogenicity of the influenza vaccine in patients undergoing cladribine treatment at different stages vs. controls. The antibody response in 90 cladribine-treated MS patients was prospectively compared with 10 control subjects receiving platform immunotherapy (NCT05019248). Serum samples were collected before and six months after vaccination. Response to vaccination was determined by the hemagglutination-inhibition test. Postvaccination seroprotection rates against influenza A were comparable in cladribine-treated patients and controls (H1N1: 94.4% vs. 100%; H3N2: 92.2% vs. 90.0%). Influenza B response was lower in the cladribine cohort (61.1% vs. 80%). The increase in geometric mean titers was lower in the cladribine group vs. controls (H1N1: +98.5 vs. +188.1; H3N2: +225.3 vs. +300.0; influenza B: +40.0 vs. +78.4); however, titers increased in both groups for all strains. Seroprotection was achieved irrespective of vaccination timing and lymphocyte subset counts at the time of vaccination in the cladribine cohort. To conclude, cladribine-treated MS patients can mount an adequate immune response to influenza independently of treatment duration and time interval to the last cladribine administration.

Pre-pandemic SARS-CoV-2-specific IFN-γ and antibody responses were low in Ugandan samples and significantly reduced in HIV-positive specimens.

Introduction: We investigated whether prior SARS-CoV-2-specific IFN-γ and antibody responses in Ugandan COVID-19 pre-pandemic specimens aligned to this population's low disease severity. Methods: We used nucleoprotein (N), spike (S), NTD, RBD, envelope, membrane, SD1/2-directed IFN-γ ELISpots, and an S- and N-IgG antibody ELISA to screen for SARS-CoV-2-specific cross-reactivity. Results: HCoV-OC43-, HCoV-229E-, and SARS-CoV-2-specific IFN-γ occurred in 23, 15, and 17 of 104 specimens, respectively. Cross-reactive IgG was more common against the nucleoprotein (7/110, 15.5%; p = 0.0016, Fishers' Exact) than the spike (3/110, 2.72%). Specimens lacking anti-HuCoV antibodies had higher rates of pre-epidemic SARS-CoV-2-specific IFN-γ cross-reactivity (p-value = 0.00001, Fishers' exact test), suggesting that exposure to additional factors not examined here might play a role. SARS-CoV-2-specific cross-reactive antibodies were significantly less common in HIV-positive specimens (p=0.017; Fishers' Exact test). Correlations between SARS-CoV-2- and HuCoV-specific IFN-γ responses were consistently weak in both HIV negative and positive specimens. Discussion: These findings support the existence of pre-epidemic SARS-CoV-2-specific cellular and humoral cross-reactivity in this population. The data do not establish that these virus-specific IFN-γ and antibody responses are entirely specific to SARS-CoV-2. Inability of the antibodies to neutralise SARS-CoV-2 implies that prior exposure did not result in immunity. Correlations between SARS-CoV-2 and HuCoV-specific responses were consistently weak, suggesting that additional variables likely contributed to the pre-epidemic cross-reactivity patterns. The data suggests that surveillance efforts based on the nucleoprotein might overestimate the exposure to SARS-CoV-2 compared to inclusion of additional targets, like the spike protein. This study, while limited in scope, suggests that HIV-positive people are less likely than HIV-negative people to produce protective antibodies against SARS-CoV-2.