Integrating population and single-cell variations in vaccine responses identifies a naturally adjuvanted human immune setpoint.

Multimodal single-cell profiling methods can capture immune cell variations unfolding over time at the molecular, cellular, and population levels. Transforming these data into biological insights remains challenging. Here, we introduce a framework to integrate variations at the human population and single-cell levels in vaccination responses. Comparing responses following AS03-adjuvanted versus unadjuvanted influenza vaccines with CITE-seq revealed AS03-specific early (day 1) response phenotypes, including a B cell signature of elevated germinal center competition. A correlated network of cell-type-specific transcriptional states defined the baseline immune status associated with high antibody responders to the unadjuvanted vaccine. Certain innate subsets in the network appeared "naturally adjuvanted," with transcriptional states resembling those induced uniquely by AS03-adjuvanted vaccination. Consistently, CD14+ monocytes from high responders at baseline had elevated phospho-signaling responses to lipopolysaccharide stimulation. Our findings link baseline immune setpoints to early vaccine responses, with positive implications for adjuvant development and immune response engineering.

Activation Dynamics and Immunoglobulin Evolution of Pre-existing and Newly Generated Human Memory B cell Responses to Influenza Hemagglutinin.

Vaccine-induced memory B cell responses to evolving viruses like influenza A involve activation of pre-existing immunity and generation of new responses. To define the contribution of these two types of responses, we analyzed the response to H7N9 vaccination in H7N9-naive adults. We performed comprehensive comparisons at the single-cell level of the kinetics, Ig repertoire, and activation phenotype of established pre-existing memory B cells recognizing conserved epitopes and the newly generated memory B cells directed toward H7 strain-specific epitopes. The recall response to conserved epitopes on H7 HA involved a transient expansion of memory B cells with little observed adaptation. However, the B cell response to newly encountered epitopes was phenotypically distinct and generated a sustained memory population that evolved and affinity matured months after vaccination. These findings establish clear differences between newly generated and pre-existing memory B cells, highlighting the challenges in achieving long-lasting, broad protection against an ever-evolving virus.

Correlates of Rotavirus Vaccine Shedding and Seroconversion in a U.S. Cohort of Healthy Infants.

BACKGROUND: Rotavirus is a leading cause of severe pediatric gastroenteritis; two highly effective vaccines are used in the US. We aimed to identify correlates of immune response to rotavirus vaccination in a US cohort. METHODS: PREVAIL is a birth cohort of 245 mother-child pairs enrolled 2017-2018 and followed for 2 years. Infant stool samples and symptom information were collected weekly. Shedding was defined as RT-PCR detection of rotavirus vaccine virus in stools collected 4-28 days after dose one. Seroconversion was defined as a threefold rise in IgA between the six-week and six-month blood draws. Correlates were analyzed using generalized estimating equations and logistic regression. RESULTS: Pre-vaccination IgG (OR=0.84, 95% CI [0.75-0.94] per 100-unit increase) was negatively associated with shedding. Shedding was also less likely among infants with a single-nucleotide polymorphism inactivating FUT2 antigen secretion ("non-secretors") with non-secretor mothers, versus all other combinations (OR 0.37 [0.16-0.83]). Of 141 infants with data, 105 (74%) seroconverted; 78 (77%) had shed vaccine virus following dose one. Pre-vaccination IgG and secretor status were significantly associated with seroconversion. Neither shedding nor seroconversion significantly differed by vaccine product. DISCUSSION: In this US cohort, pre-vaccination IgG and maternal and infant secretor status were associated with rotavirus vaccine response.

Evaluating patient immunocompetence through antibody response to pneumococcal polysaccharide vaccine using a newly developed 23 serotype multiplexed assay.

Assessing T-cell independent antibody response to polysaccharide vaccines is crucial for diagnosing humoral immune deficiencies. However, immunocompetence criteria based on S. pneumoniae vaccination remain unclear. We evaluated IgG antibody vaccine response in healthy individuals to establish interpretive criteria. Pre- and 4-week post-vaccination sera were collected from 79 adults. Antibody concentrations to PNEUMOVAX 23 serotypes were measured using a multiplexed platform. Immunocompetence was determined by fold increase in post-vaccination response, percentage of serotypes achieving 4- or 2-fold antibody ratio, and post-vaccination concentration ≥ 1.3 µg/mL. Immunogenicity varied widely across the 23 serotypes (26.6% to 94.9% for ≥4-fold increase, 51.9% to 98.7% for ≥2-fold increase). Immunocompetence based on historic criteria of ≥4-fold increase in antibody ratio to ≥70% of serotypes was low (72.2%), but increased to 98.7% with criteria of at least a 2-fold increase and/or post-vaccination concentration ≥ 1.3 µg/mL. Current criteria for assessing immunocompetence may be overly stringent and require updating.

An Exploratory Approach of Clinically Useful Biomarkers of Cvid by Logistic Regression.

Despite advancements in genetic and functional studies, the timely diagnosis of common variable immunodeficiency (CVID) remains a significant challenge. This exploratory study was designed to assess the diagnostic performance of a novel panel of biomarkers for CVID, incorporating the sum of κ+λ light chains, soluble B-cell maturation antigen (sBCMA) levels, switched memory B cells (smB) and the VISUAL score. Comparative analyses utilizing logistic regression were performed against established gold-standard tests, specifically antibody responses. Our research encompassed 88 subjects, comprising 27 CVID, 23 selective IgA deficiency (SIgAD), 20 secondary immunodeficiency (SID) patients and 18 healthy controls. We established the diagnostic accuracy of sBCMA and the sum κ+λ, achieving sensitivity (Se) and specificity (Spe) of 89% and 89%, and 90% and 99%, respectively. Importantly, sBCMA showed strong correlations with all evaluated biomarkers (sum κ+λ, smB cell and VISUAL), whereas the sum κ+λ was uniquely independent from smB cells or VISUAL, suggesting its additional diagnostic value. Through a multivariate tree decision model, specific antibody responses and the sum κ+λ emerged as independent, signature biomarkers for CVID, with the model showcasing an area under the curve (AUC) of 0.946, Se 0.85, and Spe 0.95. This tree-decision model promises to enhance diagnostic efficiency for CVID, underscoring the sum κ+λ as a superior CVID classifier and potential diagnostic criterion within the panel.

The effect of oral probiotics on response to vaccination in older adults: a systematic review of randomised controlled trials.

This systematic review evaluated the impact of oral probiotics on the immune response to vaccination in older people. A literature search was performed in three electronic databases up to January 2023. Randomised controlled trials (RCTs) conducted in older people (age ≥ 60 years) investigating oral probiotics and vaccine response outcomes were included. Characteristics and outcome data of the included studies were extracted and analysed and study quality was assessed using the Cochrane Risk of Bias Tool for randomised trials. Ten RCTs involving 1,560 participants, reported in 9 papers, were included. Nine studies involved the seasonal influenza vaccine and one a COVID-19 vaccine. All studies used lactobacilli, some in combination with bifidobacteria. Studies reported outcomes including anti-vaccine antibody titres or concentrations, seroconversion and seroprotection. When comparing antibody titres, seroprotection rate and seroconversion rate between probiotic and placebo groups expressed as a response ratio, the weighted mean values were 1.29, 1.16 and 2.00, respectively. Meta-analysis showed that probiotics increase seroconversion rates to all three strains of the seasonal influenza vaccine: odds ratio (95% confidence interval) 2.74 (1.31, 5.70; P = 0.007) for the H1N1 strain; 1.90 (1.04, 3.44; P = 0.04) for the H3N2 strain; 1.72 (1.05, 2.80; P = 0.03) for the B strain. There was a low level of heterogeneity in these findings. Several studies were at high risk of bias due to missing outcome data. Lactobacilli may improve the vaccine response, but further research is needed to be more certain of this.

High Frequency of Specific Polysaccharide Antibody Deficiency in Adults With Unexplained, Recurrent and/or Severe Infections With Encapsulated Bacteria.

BACKGROUND: Primary immunodeficiencies (PIDs) in adults are mainly revealed by recurrent and/or severe bacterial infections. The objective of this study was to evaluate a systematic research strategy of PIDs in adults with unexplained bacterial infections, with a special focus on specific polysaccharide antibody deficiency (SPAD). METHODS: In this prospective multicenter study, inclusion criteria were recurrent benign upper and lower respiratory tract infections (RTIs) for at least two years (group 1), at least one upper or lower RTI requiring hospitalization (group 2), and/or at least one invasive infection documented with encapsulated bacteria (group 3). Main exclusion criteria were all local and general conditions that could explain infections. If no PID diagnosis was made, response to polysaccharide antigens was assessed using a pneumococcal polysaccharide vaccine. RESULTS: From March 2015 to March 2020, 118 patients were included (37 males, median age of 41 years): 73, 17, and 28 in groups 1, 2, and 3, respectively. Forty-seven PIDs were diagnosed, giving an estimated frequency of 39.8% (95% confidence interval [CI] [30.4, 48.8]). SPAD was the most frequent diagnosis by far (n = 37/47, 78.7%), and was made in 23, 5, and 9 patients from groups 1 to 3, respectively. All SPAD patients received conjugate vaccines and, according to their infectious history, were on surveillance or treated with preventive antibiotics (n = 6) and/or with immunoglobulins replacement therapy (n = 10), the latter being dramatically efficient in all cases. CONCLUSIONS: Considering its high prevalence among adults with unexplained recurrent and/or severe bacterial infections, SPAD should be screened in those patients. CLINICAL TRIALS REGISTRATION: NCT02972281.

Immunogenicity of two doses of inactive COVID-19 vaccine and third booster dose mRNA vaccine in patients with cancer receiving active systemic therapy.

We aimed to evaluate the seroconversion rates after two doses of inactive COVID-19 vaccine (CoronaVac) and the benefit of a third dose mRNA vaccine booster in patients with cancer receiving active treatment. Patients with solid tumors receiving active treatment (n = 101) and patients with no-cancer (n = 48) as the control group were included in the study. All the patients and controls had received two doses of CoronaVac and a third booster dose of the mRNA vaccine (Bnt162b2). Anti-SARS-CoV-2 Spike Receptor Binding Domain IgG antibody levels after the second and third dose were measured with quantitative ELISA. The median age of the patients was 66 (IQR 60-71). 79% of the patients were receiving chemotherapy, and 21% were receiving immunotherapy at the time of vaccination. Antibody levels measured after two doses of CoronaVac were significantly lower in patients with cancer than in the control group (median 0 µg/ml [IQR 0-1.17 µg/ml] vs median 0.91 µg/ml [IQR 0-2.24 µg/ml], respectively, P = .002). Seropositivity rates were 46.5% in patients with cancer and 72.9% in the control group (P = .002). Antibody measurement was performed in 26 patients after the third dose. Seroconversion rate increased from 46.5% to 88.5% (P < .001), and the antibody titers significantly increased with the third-dose booster (median 0 µg/ml [IQR 0-1.17 µg/ml] after two doses vs 12.6 µg/ml [IQR 1.8-69.1 µg/ml] after third booster dose, P < .001). Immunogenicity of CoronaVac is low in patients with cancer receiving active treatment, and administering a third dose of an mRNA vaccine is effective in terms of improving seroconversion rates.

Boosting compromised SARS-CoV-2-specific immunity with mRNA vaccination in liver transplant recipients.

BACKGROUND & AIMS: Liver transplant recipients (LTRs) demonstrate a reduced response to COVID-19 mRNA vaccination; however, a detailed understanding of the interplay between humoral and cellular immunity, especially after a third (and fourth) vaccine dose, is lacking. METHODS: We longitudinally compared the humoral, as well as CD4+ and CD8+ T-cell, responses between LTRs (n = 24) and healthy controls (n = 19) after three (LTRs: n = 9 to 16; healthy controls: n = 9 to 14 per experiment) to four (LTRs: n = 4; healthy controls: n = 4) vaccine doses, including in-depth phenotypical and functional characterization. RESULTS: Compared to healthy controls, development of high antibody titers required a third vaccine dose in most LTRs, while spike-specific CD8+ T cells with robust recall capacity plateaued after the second vaccine dose, albeit with a reduced frequency and epitope repertoire compared to healthy controls. This overall attenuated vaccine response was linked to a reduced frequency of spike-reactive follicular T helper cells in LTRs. CONCLUSION: Three doses of a COVID-19 mRNA vaccine induce an overall robust humoral and cellular memory response in most LTRs. Decisions regarding additional booster doses may thus be based on individual vaccine responses as well as evolution of novel variants of concern. IMPACT AND IMPLICATIONS: Due to immunosuppressive medication, liver transplant recipients (LTR) display reduced antibody titers upon COVID-19 mRNA vaccination, but the impact on long-term immune memory is not clear. Herein, we demonstrate that after three vaccine doses, the majority of LTRs not only exhibit substantial antibody titers, but also a robust memory T-cell response. Additional booster vaccine doses may be of special benefit for a small subset of LTRs with inferior vaccine response and may provide superior protection against evolving novel viral variants. These findings will help physicians to guide LTRs regarding the benefit of booster vaccinations.

Antibody response to a third SARS-CoV-2 vaccine dose in recipients of an allogeneic haematopoietic cell transplantation.

Allogeneic haematopoietic cell transplantation (allo-HCT) recipients show impaired antibody (Ab) response to a standard two-dose vaccination against severe acute respiratory syndrome coronavirus-2 and currently a third dose is recommended as part of the primary vaccination regimen. By assessing Ab titres 1 month after a third mRNA vaccine dose in 74 allo-HCT recipients we show sufficient neutralisation activity in 77% of the patients. Discontinuation of immunosuppression before the third vaccine led to serological responses in 50% of low responders to two vaccinations. Identifying factors that might contribute to better vaccine responses in allo-HCT recipients is critical to optimise current vaccination strategies.

SARS-CoV-2 Vaccine Effectiveness and Breakthrough Infections Among Patients Receiving Maintenance Dialysis.

RATIONALE & OBJECTIVE: SARS-CoV-2 vaccine effectiveness and immunogenicity threshold associated with protection against COVID-19-related hospitalization or death in the dialysis population are unknown. STUDY DESIGN: Retrospective, observational study. SETTING & PARTICIPANTS: Adult patients without COVID-19 history receiving maintenance dialysis through a national dialysis provider and treated between February 1 and December 18, 2021, with follow-up through January 17, 2022. PREDICTOR: SARS-CoV-2 vaccination status. OUTCOMES: All SARS-CoV-2 infections, composite of hospitalization or death following COVID-19. ANALYTICAL APPROACH: Logistic regression was used to determine COVID-19 case rates and vaccine effectiveness. RESULTS: Of 16,213 patients receiving dialysis during the study period, 12,278 (76%) were fully vaccinated, 589 (4%) were partially vaccinated, and 3,346 (21%) were unvaccinated by the end of follow-up. Of 1,225 COVID-19 cases identified, 550 (45%) occurred in unvaccinated patients, and 891 (73%) occurred during the Delta variant-dominant period. Between the pre-Delta period and the Delta-dominant period, vaccine effectiveness rates against a severe COVID-19-related event (hospitalization or death) were 84% and 70%, respectively. In the subset of 3,202 vaccinated patients with at least one anti-spike immunoglobulin G (IgG) assessment, lower anti-spike IgG levels were associated with higher case rates per 10,000 days and higher adjusted hazard ratios for infection and COVID-19-related hospitalization or death. LIMITATIONS: Observational design, residual biases, and confounding may exist. CONCLUSIONS: Among maintenance dialysis patients, SARS-CoV-2 vaccination was associated with a lower risk of COVID-19 diagnosis and associated hospitalization or death. Among vaccinated patients, a low anti-spike IgG level is associated with worse COVID-19-related outcomes.

Rituximab-treated rheumatic patients: B cells predict seroconversion after COVID-19 boost or revaccination in initial vaccine non-responders.

OBJECTIVES: To investigate the effect of either a booster vaccine (one dose) or revaccination (two doses 3 weeks apart) on the antibody response to the COVID-19 mRNA vaccines in patients with rheumatic disease (RD) treated with rituximab (RTX) who had not produced vaccine-reactive antibodies after the initial two vaccine doses. Further, to examine if B cell levels in peripheral blood predicted seroconversion. METHODS: We included 91 RTX-treated RD patients previously vaccinated against COVID-19. Patients were offered revaccination or a single booster vaccination with an mRNA vaccine. Serum total antibodies against SARS-CoV-2 spike protein were measured before and 6 weeks after the last vaccine dose. B cells (CD19+CD45+) were measured by flow cytometry at inclusion. RESULTS: Of RD patients with undetectable SARS-CoV-2 antibody levels before inclusion, seroconversion was seen in 38% 6 weeks after the booster dose and 32% after revaccination. Patients receiving revaccination had significantly higher antibody levels than patients receiving a booster dose (P < 0.001). In both univariate and multivariate logistic regression analysis, only B cells higher than 10/µl before boost or revaccination were associated with seroconversion (P = 0.009 and P = 0.01, respectively). Seroconversion was independent of age, gender, diagnosis, cumulative RTX dose, RTX treatment time and time since last RTX treatment. CONCLUSION: Continuously impaired humoral response to mRNA vaccines was found in most RTX-treated patients after a booster dose or revaccination. Seroconversion was observed in approximately one-third of the patients. Measurable B cells before boosting or revaccination was the strongest predictor of antibody response after boost or revaccination.

Genetics and measles, mumps and rubella vaccine response in childhood and adolescence-A systematic review.

Measles, mumps and rubella (MMR) are contagious infectious diseases that can be prevented by immunization. However, MMR infections can occur in previously immunized individuals. The vaccine response is, among other factors, influenced by the combined effects of many genes. This systematic review investigates the genetic influence on measles, mumps and rubella antibody responses after childhood vaccination. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), systematic literature searches were conducted in the medical databases PubMed, EMBASE and PsycINFO. Search strings were adjusted for each database. Citations were included if they measured and compared the immune response with immunogenetics after vaccination with a vaccine containing one or more of the following components: measles, mumps and/or rubella, MMR. The measure of vaccine response studied was antibodies after vaccination. Forty-eight articles were included in the final analysis. The results suggest that genetic determinants, including host genes, and single nucleotide polymorphisms in immune-related genes influence the MMR antibody responses after vaccination. Specifically, replicated associations were found between HLA, CD46, RARB, IRF9, EIF2AK2, cytokine genes and MMR vaccine-induced humoral immune responses. This knowledge can be useful in understanding and predicting immune responses and may have implications for future vaccine strategies.

Humoral COVID-19 vaccine response in patients with NMOSD/MOGAD during anti-IL-6 receptor therapy compared to other immunotherapies.

BACKGROUND: Data on the humoral vaccine response in patients on anti-interleukin-6 (IL-6) receptor therapy remain scarce. OBJECTIVE: The main objective of our study was to investigate the humoral response after vaccination against SARS-CoV-2 in neuromyelitis optica spectrum disorder (NMOSD)/myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) patients treated with anti-IL-6 receptor therapy. Secondarily, we analyzed relapse activity timely associated with vaccination. METHODS: In this retrospective cross-sectional multicenter study, we included 15 healthy controls and 48 adult NMOSD/MOGAD patients without previous COVID-19 infection. SARS-CoV-2 spike protein antibody titers during anti-IL-6 receptor therapy were compared to anti-CD20 antibody therapy, oral immunosuppressants, and to nonimmunosuppressed individuals. RESULTS: We observed 100% seroconversion in the anti-IL-6 receptor treatment group. Titers of SARS-CoV-2 spike protein antibodies were lower compared to healthy controls (720 vs 2500 binding antibody units (BAU)/mL, p = 0.004), but higher than in the anti-CD20 (720 vs 0.4 BAU/mL, p < 0.001) and comparable to the oral immunosuppressant group (720 vs 795 BAU/mL, p = 1.0). We found no association between mRNA-based vaccines and relapse activity in patients with or without immunotherapy. CONCLUSIONS: Despite being lower than in healthy controls, the humoral vaccine response during anti-IL-6 receptor therapy was evident in all patients and substantially stronger compared to anti-CD20 treatment. No relevant disease activity occurred after mRNA vaccination against SARS-CoV-2.

Anti-SARS-CoV-2 antibodies following vaccination are associated with lymphocyte count and serum immunoglobulins in SLE.

OBJECTIVES: Patients with Systemic Lupus Erythematosus are known to have dysregulated immune responses and may have reduced response to vaccination against COVID-19 while being at risk of severe COVID-19 disease. The aim of this study was to identify whether vaccine responses were attenuated in SLE and to assess disease- and treatment-specific associations. METHODS: Patients with SLE were matched by age, sex and ethnic background to healthcare worker healthy controls (HC). Anti-SARS-CoV-2 spike glycoprotein antibodies were measured at 4-8 weeks following the second COVID-19 vaccine dose (either BNT162b2 or ChAdOx1 nCoV-19) using a CE-marked combined ELISA detecting IgG, IgA and IgM (IgGAM). Antibody levels were considered as a continuous variable and in tertiles and compared between SLE patients and HC and associations with medication, disease activity and serological parameters were determined. RESULTS: Antibody levels were lower in 43 SLE patients compared to 40 HC (p < 0.001). There was no association between antibody levels and medication, lupus disease activity, vaccine type or prior COVID infection. Higher serum IgA, but not IgG or IgM, was associated with being in a higher anti-SARS-CoV-2 antibody level tertile (OR [95% CI] 1.820 [1.050, 3.156] p = 0.033). Similarly, higher lymphocyte count was also associated with being in a higher tertile of anti-SARS-CoV-2 (OR 3.330 [1.505, 7.366] p = 0.003). CONCLUSION: Patients with SLE have lower antibody levels following 2 doses of COVID-19 vaccines compared to HC. In SLE lower lymphocyte counts and serum IgA levels are associated with lower antibody levels post vaccination, potentially identifying a subgroup of patients who may therefore be at increased risk of infection.

Immune responses to SARS-CoV-2 vaccines in celiac disease.

BACKGROUND AND AIMS: SARS-CoV-2 infection and development of the disease COVID-19 is a serious threat to our society. Effective vaccines have now entered the market, but most patient populations were not included in the registration clinical trials. There is evidence that patients with celiac disease (CeD) have reduced effect of vaccines such as the hepatitis B vaccine. Hence, we investigated the humoral response to SARS-CoV-2 vaccines (Chadox1, Comirnaty and Spikevax) in CeD patients and healthy controls. METHODS: CeD patients from a patient registry at Oslo University Hospital were invited to donate serum samples before and after vaccination. We sent out 1537 invitations and received paired samples from 85 individuals. These were compared with similar samples from 238 healthy controls. Sera were analyzed for antibodies to the Spike protein from SARS-CoV2 and the receptor-binding domain. The results where then converted into binding antibody units (BAU)/ml to compare. RESULTS: Prevaccination samples showed that very few patients had been earlier exposed to Sars-CoV2 and the antibody levels were low. Postvaccination analysis showed overlap of antibody levels between CeD and healthy controls. On average, the CeD patient group had 5555.0 BAU/ml (330.1 SD) while the average in healthy controls was 5419 (184.7 SD). CONCLUSION: The humoral response to SARS-CoV-2 vaccines in CeD patients is similar to that observed in healthy controls.

Assessment of the influence of ABO blood groups on oral cholera vaccine immunogenicity in a cholera endemic area in Zambia.

BACKGROUND: Histo-blood group antigens (HBGAs) which include the ABO and Lewis antigen systems have been known for determining predisposition to infections. For instance, blood group O individuals have a higher risk of severe illness due to V. cholerae compared to those with non-blood group O antigens. We set out to determine the influence that these HBGAs have on oral cholera vaccine immunogenicity and seroconversion in individuals residing within a cholera endemic area in Zambia. METHODOLOGY: We conducted a longitudinal study nested under a clinical trial in which samples from a cohort of 223 adults who were vaccinated with two doses of Shanchol™ and followed up over 4 years were used. We measured serum vibriocidal geometric mean titers (GMTs) at Baseline, Day 28, Months 6, 12, 24, 30, 36 and 48 in response to the vaccine. Saliva obtained at 1 year post vaccination was tested for HBGA phenotypes and secretor status using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Of the 133/223 participants included in the final analysis, the majority were above 34 years old (58%) and of these, 90% were males. Seroconversion rates to V. cholerae O1 Inaba with non-O (23%) and O (30%) blood types were comparable. The same pattern was observed against O1 Ogawa serotype between non-O (25%) and O (35%). This trend continued over the four-year follow-up period. Similarly, no significant differences were observed in seroconversion rates between the non-secretors (26%) and secretors (36%) against V. cholerae O1 Inaba. The same was observed for O1 Ogawa in non-secretors (22%) and the secretors (36%). CONCLUSION: Our results do not support the idea that ABO blood grouping influence vaccine uptake and responses against cholera.

Neutralizing Antibody Responses Among Residents and Staff of Long-Term Care Facilities in the State of New Jersey During the First Wave of the COVID-19 Pandemic.

Expanding a previous study of the immune response to SARS-CoV-2 in 10 New Jersey long-term care facilities (LTCFs) during the first wave of the pandemic, this study characterized the neutralizing antibody (NAb) response to infection and vaccination among residents and staff. Sera from the original study were tested using the semi-quantitative enzyme-linked immunosorbent cPass neutralization-antibody detection assay. Almost all residents (97.8%) and staff (98.1%) who were positive for IgG S antibody to the spike protein were positive for NAb. In non-vaccinated subjects with a history of infection (positive polymerase chain reaction (PCR) or antigen test), the distribution of mean intervals from infection to serology date was not significantly different for S antibody positives versus negatives. More than 80% of both were positive at 10 months. Similarly, the mean NAb titer for residents and staff was not associated with interval from PCR/antigen positive to serology date, F = 0.1.01, Pr > F = 0.4269 and F = 0.77, Pr > F = 0.6548 respectively. Titers remained high as the interval reached 10 months. In vaccinees who had no history of infection, the NAb titer was near the test maximum when the serum was drawn seven or more days after the second vaccine dose. In staff the mean NAb titer increased significantly as the vaccine number increased from one to two doses, F = 11.69, Pr > F < 0.0001. NAb titers to SARS-CoV-2 in residents and staff of LTCFs were consistently high 10 months after infection and after two doses of vaccine. Ongoing study is needed to determine whether this antibody provides protection as the virus continues to mutate.

The predictive role of NF-κB-mediated pro-inflammatory cytokine expression levels in hepatitis B vaccine response.

Hepatitis B virus (HBV) infection is a global health problem leading to cirrhosis, hepatocellular carcinoma, and liver failure. The Hepatitis B vaccine plays a significant role in reducing the incidence of HBV worldwide. Approximately 5-10% of vaccinated people do not produce protective antibody levels. Nuclear factor kappa B (NF­κB) mediates inflammatory responses through pro-inflammatory cytokines. However, the role of the NF­κB signaling pathway and its association with pro-inflammatory cytokines in hepatitis B vaccine response is unclear. We aimed to assess changes in the IL1A, IL6, IL12A, TNF-α, and NFκB1 expression levels in the non-responder and responder. A total of 32 non-responders and 36 responders were included in the study. The expression level of determined genes was analyzed by RT-PCR. Our results showed that IL1A, IL6, IL12A, and NFκB1 mRNA levels significantly increased in the non-responders compared to the responders (p < .01). Furthermore, there was a significant correlation between IL1A, IL6, TNF-α, and NFκB1 in the non-responder and responders. In conclusion, inflammatory signaling pathways may play an important role in response to HBV vaccine. Therefore, NF­κB signaling and associated pro-inflammatory cytokine mRNA levels could predict hepatitis B vaccine response. However, the underlying molecular mechanisms of hepatitis B vaccine immunity need further investigation.

SARS-CoV-2 vaccine response in CAR T-cell therapy recipients: A systematic review and preliminary observations.

Evolving data suggest that SARS-CoV-2 vaccine responses are blunted in allogeneic hematopoeitic cell transplant (HCT) recipients. Responses to the vaccine in chimeric antigen receptor T-cell (CAR-T) therapy are unknown and are likely to be even more diminished. We manually searched vital databases and identified 5 studies that have so far reported COVID-19 vaccine response in a total of 70 CAR-T recipients. The cumulative humoral response rate across all 5 studies was 31%. However, the results are not generalizable due to non-standardized units of humoral response measurement and a lack of external validation. Heterogeneity existed in studies regarding the timing of vaccination post-CAR-T, intervals between the vaccine doses, platforms of response assessment, vaccine platforms, and pre-vaccine immune status. CAR-T-related factors that independently impact vaccine response to prevent COVID-19 have further been reviewed. We conclude that the results must be interpreted with caution given the limitations of small sample sizes, differences in immunoassays, lack of standard definitions and clinical correlates of SARS-CoV-2 immune response, and lack of cellular responses. Until large-scale, homogenous prospective data become available, these preliminary observations will help transplant and infectious disease clinicians with their decision-making while providing care to this profoundly immunosuppressed cohort of patients.