Evaluating the effect of BCG vaccination for non-specific protection from infection in senior citizens during the COVID-19 pandemic: A randomised clinical trial.

OBJECTIVES: The Bacillus Calmette-Guérin (BCG) vaccine may induce non-specific protection against unrelated infections. We tested the effect of BCG on the risk of infections among Danish senior citizens. METHODS: Single-blinded randomised controlled trial including 1676 volunteers >65 years. Participants were randomised 1:1 to BCG or placebo and followed for 12 months. The primary outcome was acute infection leading to medical contact. Secondary outcomes were verified SARS-CoV-2 infection, self-reported respiratory symptoms, and all-cause hospitalisation. Data was analysed using Cox regression models, estimating hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: The incidence of acute infection was 52.1 and 58.2 per 100 person-years for BCG and placebo, respectively (HR=0.89, 95% CI=0.78-1.02). There was no effect of BCG on SARS-CoV-2 infections (0.97, 0.75-1.26) or all-cause hospitalisations (1.10, 0.80-1.50), but BCG was associated with more respiratory symptoms (1.21, 1.10-1.33). BCG reduced the incidence of acute infections among participants <75 years (0.82, 0.70-0.95) but not among those >75 years (1.14, 0.88-1.47). In participants, who were COVID-19 vaccinated before enrolment, BCG was associated with lower incidence of acute infections (0.65, 0.50-0.85). CONCLUSION: BCG did not reduce risk of acute infections among Danish seniors overall, but the effect was modified by age group and COVID-19 vaccination. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04542330) and EU Clinical Trials Register (EudraCT number 2020-003904-15). Full trial protocol is available at ClinicalTrials.gov. SUMMARY: In a randomised clinical trial among Danish senior citizens, BCG vaccination did not reduce the overall risk of acute infection, but BCG was associated with reduced risk in participants <75 years and participants who received COVID-19 vaccines prior to enrolment.

Barriers and facilitators to routine revaccination among adult Hematopoietic Cell Transplant survivors in the United States: A convergent mixed methods analysis.

BACKGROUND: Hematopoietic cell transplant (HCT) survivorship care includes recommendations for post-HCT revaccination to restore immunity to vaccine-preventable diseases (VPDs). However, not all survivors agree to be vaccinated. No existing studies have comprehensively reported barriers and facilitators to adult HCT survivors completing revaccination. METHODS: A cross-sectional survey of 194 adult HCT survivors was analyzed using convergent mixed methods. The analysis used various statistical methods to determine the prevalence of barriers and facilitators and the association between revaccination and the number and specific type of barriers and facilitators. Content analysis was applied to open-ended item responses. Integrated analysis merged quantitative and qualitative findings. RESULTS: The most frequent barriers included the inability to receive live vaccines because of immunosuppression, identifying a suitable community location for administering childhood vaccines to adults, and delayed immune recovery. The most frequent facilitators were having healthcare insurance and a clear calendar of the revaccination schedule. Complete revaccination rates were lower with each additional reported barrier (OR = 0.58; 95% CI 0.459-0.722) and higher with each additional reported facilitator (OR = 1.31; 95% CI 1.05-1.63). Content analysis suggested that most barriers were practical issues. One significant facilitator highlighted by respondents was for the transplant center to coordinate and serve as the vaccination location for revaccination services. Merged analysis indicated convergence between quantitative and qualitative data. CONCLUSION: Practical barriers and facilitators played a consequential role in revaccination uptake, and survivors would like to be revaccinated at the transplant center.

Vaccine hesitancy and routine revaccination among adult HCT survivors in the United States: A convergent mixed methods analysis.

Revaccination to restore immunity to vaccine-preventable diseases (VPDs) is essential risk mitigation in the prevention of infectious morbidity and mortality after hematopoietic cell transplantation (HCT). However, revaccination rates have been shown to be insufficient and to what extent vaccine hesitancy contributes to survivors not becoming fully revaccinated is unknown. We performed a cross-sectional, mixed methods survey-based study to explore how vaccine hesitancy influences revaccination among US adult HCT survivors who were 2 to 8 years after transplant. Participants were asked to complete the Vaccination Confidence Scale (VCS) and open-ended survey items regarding vaccine confidence. The survey response rate was 30 %; among 332 respondents, vaccine confidence was high in 69 %, medium in 20 %, and low in 11 %. On multivariable analysis, four factors associated with high vaccine confidence were: predominantly Democrat zip codes (per 2020 election results), ability to pay for revaccination out of pocket, receipt of pre-HCT adult vaccines, and receipt of COVID-19 vaccines. From 189 participants who also answered open-ended items, 14 themes associated with vaccine confidence were identified and collapsed into 4 categories based on the VCS: Benefits, Harms, Trust, and Other. Merged analysis showed congruence between VCS scores and open-ended survey responses and created a narrative about the relative importance of the constructs when approaching revaccination by vaccine confidence level. These findings significantly expand our knowledge of how vaccine hesitancy influences revaccination uptake among US adult HCT survivors. Population-specific interventions to approach vaccine-hesitant survivors should be developed and tested.

Policies for the immunization against serogroup B meningococcus for adolescents immunized during the first two years of life: A mini review.

Two vaccines are available to prevent serogroup B meningococcal disease, i.e. the four-component meningococcal serogroup B vaccine (4CMenB) and the bivalent-factor-H-binding-protein meningococcal serogroup B vaccine (MenB-fHbp). Currently, 4CMenB is offered as part of routine infant immunization schedules. Available immunogenicity data showed a progressive decline in protective serum bactericidal antibodies (SBA) titers, with a re-enhancement following a booster dose during infancy. Responses did not seem to be long-lasting and vaccinated individuals might be at risk of meningococcal diseases during adolescence. Only one study evaluated the possibility to administer a single booster dose to immunocompetent adolescents who received a primary series during infancy. Despite a high proportion of enrollees achieving protective SBA levels 28 days post-booster, titers tended to decrease 1 year after. Immunocompetent adolescents who received a primary series and a booster during the first two years of life might rather benefit from re-vaccination against MenB; current evidence does not support the possibility of a booster.

Safety profile of BCG revaccination for COVID prevention among elderly individuals in India.

BCG vaccination is known to be safe in infants and a part of immunization schedule in high tuberculosis (TB) burden countries. In the conquest to bring down the severity of the COVID 19 pandemic, many drugs were repurposed in research mode including BCG vaccination/revaccination in various populations. We did a study among the elderly population (>60 years of age) to assess the role of BCG revaccination in preventing the severity of COVID 19 disease. Live attenuated BCG vaccine was given to the willing participants and were followed up for 6 months to estimate COVID19 incidence, understand severity and immunogenicity profile. A total of 48 serious adverse events (SAE) were reported among 1566 elders, none of them had more than one SAE. None of the SAEs were related to the BCG revaccination. Among the 372 adverse events reported, 96% were local reactions at the vaccine site and resolved on its own. BCG revaccination appeared to be safe and could be explored further if repurposing studies were planned for other diseases.

Associations Between Demographic Factors, Clinical Variables, Social Determinants of Health, Vaccine Hesitancy, Vaccine Behavior, and Revaccination Status: A Survey of Adult HCT Survivors in the United States.

Comprehensive survivorship care after hematopoietic cell transplantation (HCT) includes revaccination to restore immunity to vaccine-preventable diseases (VPDs). There is complexity to revaccination in this setting, and revaccination rates are sub-optimal. HCT survivors are at high-risk for morbidity and mortality from infections including VPDs, underscoring the importance of interventions to improve revaccination rates among survivors. Determining associations between survivor characteristics and revaccination uptake may guide interventions. The overall study objective was to advance our understanding of factors influencing revaccination uptake among adult HCT survivors living in the United States The specific study aims were to: (1) determine the prevalence of adult survivors who are completely, partially, or not revaccinated at 2 to 8 years after HCT and (2) examine associations between demographic variables, social determinants of health, clinical variables, past vaccination behaviors, vaccine hesitancy (Vaccination Confidence Scale), and revaccination status in adult HCT survivors. This study employed a one-time cross-sectional revaccination survey of adults who were surviving 2 to 8 years after HCT and living in the United States. The survey was sent to eligible survivors in the Fred Hutchinson Cancer Center Long-term Follow-up research cohort. The point prevalence of revaccination outcomes was determined from all the respondents (n = 338), differences in intent to revaccinate for people not yet fully revaccinated were explored using Fisher's exact test (n = 126), and associations were examined between revaccination outcomes and predictors using multivariable logistic regression (n = 292). Survey response rate was 30%. Among respondents, 62% were completely revaccinated, 33% were partially revaccinated, and 4% were not revaccinated. Most respondents (77%) who were not yet fully revaccinated planned to complete the revaccination protocol. However, fewer not-revaccinated respondents than partially revaccinated respondents planned to complete revaccination (50% versus 80%, P = .032). Factors associated with incomplete revaccination were shorter time from HCT, inadequate immune reconstitution, and not having received all childhood vaccines as a child. Our analysis has identified multiple variables associated with revaccination outcomes, indicating the potential for interventions to enhance post-HCT revaccination rates. Since many survivors cannot be revaccinated promptly due to delayed immune recovery, clinicians should iteratively re-evaluate for revaccination readiness as long as it takes to ensure eventual revaccination. Broader efforts by the healthcare community to increase childhood vaccine uptake might eventually support revaccination uptake. Future research that builds on these findings should focus on intervention testing.

Estimating the Potential Public Health Value of BCG Revaccination.

An upcoming trial may provide further evidence that adolescent/adult-targeted BCG revaccination prevents sustained Mycobacterium tuberculosis infection, but its public health value depends on its impact on overall tuberculosis morbidity and mortality, which will remain unknown. Using previously calibrated models for India and South Africa, we simulated BCG revaccination assuming 45% prevention-of-infection efficacy, and we evaluated scenarios varying additional prevention-of-disease efficacy between +50% (reducing risk) and -50% (increasing risk). Given the assumed prevention-of-infection efficacy and range in prevention-of-disease efficacy, BCG revaccination may have a positive health impact and be cost-effective. This may be useful when considering future evaluations and implementation of adolescent/adult BCG revaccination.

Effectiveness of different booster vaccine combinations against SARS-CoV-2 during a six-month follow-up in Mexico and Argentina.

Introduction: Given the limited number of patients in Latin America who have received a booster dose against the COVID-19, it remains crucial to comprehend the effectiveness of different vaccine combinations as boosters in real-world scenarios. This study aimed to assess the real-life efficacy of seven different vaccine schemes against COVID-19, including BNT162b2, ChAdOx1-S, Gam-COVID-Vac, and CoronaVac as primary schemes with either BNT162b2 or ChAdOx1-S as booster vaccines. Methods: In this multicentric longitudinal observational study, participants from Mexico and Argentina were followed for infection and SARS-CoV-2 Spike 1-2 IgG antibodies during their primary vaccination course and for 185 days after the booster dose. Results: A total of 491 patients were included, and the booster dose led to an overall increase in the humoral response for all groups. Patients who received BNT162b2 exhibited the highest antibody levels after the third dose, while those with primary Gam-COVID-Vac maintained a higher level of antibodies after six months. Infection both before vaccination and after the booster dose, and Gam-COVIDVac + BNT162b2 combination correlated with higher antibody titers. Discussion: The sole predictor of infection in the six-month follow-up was a prior COVID-19 infection before the vaccination scheme, which decreased the risk of infection, and all booster vaccine combinations conveyed the same amount of protection.

The effectiveness of revaccination with pneumococcal polysaccharide vaccine for preventing pneumococcal disease in older adults in England: A population-based cohort study.

BACKGROUND: Pneumococcal disease in older adults in the United Kingdom is rising despite immunisation. A key gap in the literature is the clinical effectiveness of revaccination with the pneumococcal polysaccharide vaccine (PPV23). METHODS: A cohort study was performed in England, using electronic medical records in the Clinical Practice Research Datalink. Individuals aged ≥64 years and vaccinated with PPV23 were included. Rates of hospitalised pneumonia (HP) and invasive pneumococcal disease (IPD) were compared between individuals receiving a single PPV23 dose versus those receiving two doses using multi-level Cox proportional hazards models. Propensity score weighting was performed to minimise the effect of confounding covariates across the comparison groups. RESULTS: Between 2006 and 2019, there were 462 505 eligible participants. Of those, 6747 (1·5 %) received revaccination. Two doses compared to one dose was associated with an increased risk of HP (adjusted Hazard Ratio [aHR] 1·95; 95 %CI 1·74-2·20) and IPD (aHR 1·44; 95 %CI 1·41-1·46). In participants aged 64-74 years PPV23 revaccination was associated with more IPD (aHR 2·02; 95 %CI 1·75-2·33) and HP (aHR 1·46; 95 %CI 1·42-1.49). In those aged ≥75 years PPV23 revaccination was associated with more HP (aHR 1·12; 95 %CI 1·08-1·16) with no statistically significant difference detected in risk of IPD (aHR 1·20; 95 %CI 0·94-1·52). CONCLUSIONS: No clear benefit of PPV23 revaccination was measured in older adults in this observational study. The small proportion of revaccinated subjects limits the strength of the conclusions. Further research evaluating the clinical effectiveness of PPV23 revaccination is required.

Bacillus Calmette-Guérin (BCG) Revaccination and Protection Against Tuberculosis: A Systematic Review.

Bacillus Calmette-Guérin (BCG) vaccination remains a cornerstone in global efforts to combat tuberculosis (TB), a persistent public health threat worldwide. The purpose of this systematic review is to find out how well BCG revaccination protects against TB. This systematic review synthesized recent studies investigating the efficacy of BCG vaccination in preventing TB infection and disease. A total of 15 relevant publications were identified through a comprehensive search across multiple databases, including Cochrane Library, PubMed, Medline, and Scopus. The inclusion criteria encompassed studies involving humans, written in English, and categorized as case-control, cohort, meta-analysis, or full-text. Studies were selected based on their relevance to BCG revaccination and protection against TB, and a standardized data extraction form was used to gather pertinent information from each study. Quality assessment was conducted using established tools to evaluate the rigor, study design, and risk of bias in each included study. The findings revealed significant insights into BCG's effectiveness across different populations and age groups. Several studies demonstrated a substantial reduction in latent TB infection (LTBI) and incidence rates of TB following BCG vaccination. However, the protective efficacy of BCG revaccination varied across studies and populations, with some indicating modest protection against TB disease development, particularly in high-risk populations like healthcare workers. Furthermore, investigations into the immunological mechanisms underlying BCG's protective efficacy provided valuable insights into cytokine/chemokine profiles and immunomodulatory properties.

Surname order and revaccination intentions during the COVID-19 pandemic.

Teachers in Japanese schools employ alphabetical surname lists that call students sooner, with surnames appearing early on these lists. We conducted Internet surveys nearly every month from March 2020 to September 2022 with the same participants, wherein we asked participants where the alphabetical columns of their childhood and adult surnames were located. We aimed to identify how surname order is important for the formation of noncognitive skills. During the data collection period, the COVID-19 vaccines became available; Japanese people could receive their third dose starting in December 2021. The 19th wave of the survey was conducted in January 2022. Therefore, to examine how a surname's alphabetical order could influence intention to revaccinate, we used a subsample of data from December 2021 to September 2022. The major findings were as follows. Women with early surnames had an approximately 4% stronger likelihood of having such intentions than men with early surnames. Early name order was more strongly correlated with revaccination intention among women than among men. The surname effect for women was larger when a mixed-gender list was used compared with when it was not used. This effect was only observed for childhood surnames and not for adult surnames.

Facilitators and Barriers to Successful Revaccination after Hematopoietic Stem Cell Transplantation among Adult Survivors: A Scoping Review.

Post-transplantation revaccination uptake of childhood vaccines in adult hematopoietic stem cell transplantation (HSCT) survivors is suboptimal, increasing the risk of infectious morbidity and mortality within this population. We systematically reviewed the literature for factors related to revaccination uptake, as well as the barriers and facilitators that affect successful revaccination. We conducted a scoping review searching PubMed, CINAHL, Embase, and Web of Science in March 2023. Two independent reviewers performed study selection using the complete dual review process. Data were extracted using a standard form. Factors were characterized as demographic, clinical, or social determinants of health that affected revaccination uptake. Barriers and facilitators were categorized using the constructs from the World Health Organization Behavioural and Social Drivers Framework. Our searches yielded 914 sources, from which 15 publications were selected (5 original research and 10 quality improvement initiatives). More than one-half of the reports listed factors associated with poorer uptake, predominately clinical factors, followed by social determinants of health, then demographic factors. Nearly all the reports described barriers to successful revaccination uptake, with most of these falling into the "practical issues" construct. Most of the reports described facilitators, nearly all related to health care system improvements associated with improved revaccination uptake. Although this review provides a good starting point for understanding impediments to successful revaccination after HSCT, this review reveals that we lack sufficient evidence to drive targeted interventions to improve uptake. More research is needed, focusing on survivors' voices to inform our knowledge of barriers and facilitators to complete revaccination after HSCT, exploring behavioral and social drivers within this population, and examining the care delivery models that may complicate vaccine delivery in this population.

The safety of BCG revaccination in the context of COVID-19.

The bacille Calmette-Guérin (BCG) vaccine is administered in many countries as part of their vaccination schedules. Epidemiologic studies have suggested a possible benefit of this vaccine in the context of the COVID-19 pandemic and other respiratory infections. We aimed to assess the safety of this intervention in BCG-primed adults. Adult health care workers (n = 451) received a single intradermal application of the BCG vaccine (Tokyo 172 strain) in the deltoid region of the right arm. Follow-up (30 days) calls and clinical inspections were guided using a standardized data sheet to assess local and systemic reactions. Early local reactions were common at 24 h and 7 days, such as erythema (74.9%, 69.2%), induration (55.7%, 59%), a papule (53.4%, 47.7%), and edema (48.3%, 38.1). Local symptoms (pruritus 44.8%, heat 16.2%, and pain 34.8%) were less frequent at day 7. Late expected reactions (14 and 30 days) included the formation of crusts (39.6% and 63.9%), a pustule (36.6% and 17%), or ulcers (28.8% and 17.7%). Severe reactions were limited to subcutaneous abscesses (2%) and lymphadenitis (<1%).

Safety of BCG vaccination and revaccination in healthcare workers.

BCG vaccination and revaccination are increasingly being considered for the protection of adolescents and adults against tuberculosis and, more broadly, for the off-target protective immunological effects against other infectious and noninfectious diseases. Within an international randomized controlled trial of BCG vaccination in healthcare workers (the BRACE trial), we evaluated the incidence of local and serious adverse events, as well as the impact of previous BCG vaccination on local injection site reactions (BCG revaccination). Prospectively collected data from 99% (5351/5393) of participants in Australia, Brazil, Spain, The Netherlands and the UK was available for analysis. Most BCG recipients experienced the expected self-limiting local injection site reactions (pain, tenderness, erythema, swelling). BCG injection site itch was an additional common initial local symptom reported in 49% of BCG recipients. Compared to BCG vaccination in BCG-naïve individuals, BCG revaccination was associated with increased frequency of mild injection site reactions, as well as earlier onset and shorter duration of erythema and swelling, which were generally self-limiting. Injection site abscess and regional lymphadenopathy were the most common adverse events and had a benign course. Self-resolution occurred within a month in 80% of abscess cases and 100% of lymphadenopathy cases. At a time when BCG is being increasingly considered for its off-target effects, our findings indicate that BCG vaccination and revaccination have an acceptable safety profile in adults.

Antigenic Cartography Indicates That the Omicron BA.1 and BA.4/BA.5 Variants Remain Antigenically Distant to Ancestral SARS-CoV-2 after Sputnik V Vaccination Followed by Homologous (Sputnik V) or Heterologous (Comirnaty) Revaccination.

The rapid emergence of evasive SARS-CoV-2 variants is an ongoing challenge for COVID-19 vaccinology. Traditional virus neutralization tests provide detailed datasets of neutralization titers against the viral variants. Such datasets are difficult to interpret and do not immediately inform of the sufficiency of the breadth of the antibody response. Some of these issues could be tackled using the antigenic cartography approach. In this study, we created antigenic maps using neutralization titers of sera from donors who received the Sputnik V booster vaccine after primary Sputnik V vaccination and compared them with the antigenic maps based on serum neutralization titers of Comirnaty-boosted donors. A traditional analysis of neutralization titers against the WT (wild-type), Alpha, Beta, Delta, Omicron BA.1, and BA.4/BA.5 variants showed a significant booster humoral response after both homologous (Sputnik V) and heterologous (Comirnaty) revaccinations against all of the studied viral variants. However, despite this, a more in-depth analysis using antigenic cartography revealed that Omicron variants remain antigenically distant from the WT, which is indicative of the formation of insufficient levels of cross-neutralizing antibodies. The implications of these findings may be significant when developing a new vaccine regimen.

Clinical assessment of a point-of-care assay to determine protective vaccinal antibody titers to canine viral diseases.

Guidelines recommend that dogs are vaccinated for canine distemper virus (CDV), canine parvovirus (CPV), and canine adenovirus (CAV) every 3 years. Alternatively, their antibody titers are measured and vaccines given when titers fall below a protective threshold. In this study, a point-of-care (POC) assay was compared to hemagglutination inhibition (for CPV) and virus neutralization (for CAV and CDV) assays to predict the need for revaccination Ninety-two dogs presented for vaccination were enrolled. The POC assay indicated protective titers against CDV in 79/80, CPV in 89/90, and CAV in 91/91 dogs with reference standard antibody measurements that were over a protective threshold. The sensitivity of the POC assay for to detect protective concentrations of CDV antibodies was 99% (95% confidence interval [CI 95%], 93.3-99.9%). Ten dogs were falsely considered protected against CDV by the POC assay with a specificity of 17% (CI 95%, 3.0-44.8%). The sensitivity of the POC assay for protective concentrations of CPV titers was 99% (CI 95%, 93.9-99.9%). The sensitivity of the POC assay to detect protective concentrations of CAV antibodies was 100% (CI 95%, 95.9-100%). Only classifying high-positive CDV and CPV titers on the POC assay as protective improved assay specificity to 100%, but sensitivity decreased to 51% and 76% respectively. This POC assay had a high sensitivity for the detection of protective antibody titers; however, some dogs were falsely categorized as protected, especially for CDV.

Anaphylactic reactions after COVID-19 vaccination in Germany.

. For the COVID-19 vaccines used in Germany, severe allergic (anaphylactic) reactions after vaccination have been reported in very rare cases. While Comirnaty and Spikevax are mRNA vaccines, Vaxzevria and Jcovden comprise vector vaccines, and Nuvaxovid a recombinant spike protein vaccine. The reporting rate of anaphylaxis after mRNA vaccination was higher in females receiving their first vaccination dose, with 0.97 and 1.12 reports per 100,000 vaccinations for Comirnaty and Spikevax, respectively, compared with vaccinated males and subsequent vaccinations. The Paul-Ehrlich-Institut (PEI) investigated 106 responses of 321 cases of confirmed anaphylactic reactions concerning subsequent allergy testing and revaccination with a COVID-19 vaccine. The collected data indicate that only a small proportion of cases (22%) were IgE-mediated reactions. A large proportion (73%) of patients could be revaccinated under precautionary measures without recurrence of anaphylaxis. The pathomechanism of the majority of anaphylactic reactions remains unclear and should be investigated in further studies.

A prospective study of cellular immune response to booster COVID-19 vaccination in multiple sclerosis patients treated with a broad spectrum of disease-modifying therapies.

BACKGROUND: Most people with Multiple Sclerosis (pwMS) are subjected to immunomodulatory disease-modifying treatments (DMTs). As a result, immune responses to COVID-19 vaccinations could be compromised. There are few data on cellular immune responses to the use of COVID-19 vaccine boosters in pwMS under a broad spectrum of DMTs. METHODS: In this prospective study, we analysed cellular immune responses to SARS-CoV-2 mRNA booster vaccinations in 159 pwMS with DMT, including: ocrelizumab, rituximab, fingolimod, alemtuzumab, dimethyl fumarate, glatiramer acetate, teriflunomide, natalizumab and cladribine. RESULTS: DMTs, and particularly fingolimod, interact with cellular responses to COVID-19 vaccination. One booster dose does not increase cellular immunity any more than two doses, except in the cases of natalizumab and cladribine. SARS-CoV-2 infection combined with two doses of vaccine resulted in a greater cellular immune response, but this was not observed after supplementary booster jabs. Ocrelizumab-treated pwMS who had previously received fingolimod did not develop cellular immunity, even after receiving a booster. The time after MS diagnosis and disability status negatively correlated with cellular immunity in ocrelizumab-treated pwMS in a booster dose cohort. CONCLUSIONS: After two doses of SARS-CoV-2 vaccination, a high response yield was achieved, except in patients who had received fingolimod. The effects of fingolimod on cellular immunity persisted for more than 2 years after a change to ocrelizumab (which, in contrast, conserved cellular immunity). Our results confirmed the need to find alternative protective measures for fingolimod-treated people and to consider the possible failure to provide protection against SARS-CoV-2 when switching from fingolimod to ocrelizumab.

The impact of BCG dose and revaccination on trained immunity.

The innate immune system can display heterologous memory-like responses termed trained immunity after stimulation by certain vaccinations or infections. In this randomized, placebo-controlled trial, we investigated the modulation of Bacille Calmette-Guérin (BCG)-induced trained immunity by BCG revaccination or high-dose BCG administration, in comparison to a standard dose. We show that monocytes from all groups of BCG-vaccinated individuals exerted increased TNFα production after ex-vivo stimulation with various unrelated pathogens. Similarly, we observed increased amounts of T-cell-derived IFNγ after M. tuberculosis exposure, regardless of the BCG intervention. NK cell cytokine production, especially after heterologous stimulation with the fungal pathogen Candida albicans, was predominantly boosted after high dose BCG administration. Cytokine production capacity before vaccination was inversely correlated with trained immunity. While the induction of a trained immunity profile is largely dose- or frequency independent, baseline cytokine production capacity is associated with the magnitude of the innate immune memory response after BCG vaccination.

One- and Two-Dose Vaccinations With Modified Vaccinia Ankara-Bavarian Nordic Induce Durable B-Cell Memory Responses Comparable to Replicating Smallpox Vaccines.

BACKGROUND: Although modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccination is approved for smallpox and monkeypox prevention, immunological persistence and booster effects remain undescribed. METHODS: Participants naive to smallpox vaccination were randomized to 1 dose MVA-BN (1×MVA, n = 181), 2 doses MVA-BN (2×MVA, n = 183), or placebo (n = 181). Participants with previous smallpox vaccination received 1 MVA-BN booster (HSPX, n = 200). Subsets of the formerly naive groups (approximately 75 each) received an MVA-BN booster 2 years later. RESULTS: Neutralizing antibody (nAb) geometric mean titers (GMTs) increased from 1.1 (baseline, both naive groups) to 7.2 and 7.5 (week 4, 1×MVA and 2×MVA, respectively), and further to 45.6 (week 6, 2×MVA after second vaccination). In HSPX, nAb GMT rapidly increased from 21.6 (baseline) to 175.1 (week 2). At 2 years, GMTs for 1×MVA, 2×MVA, and HSPX were 1.1, 1.3, and 10.3, respectively. After boosting in the previously naive groups, nAb GMTs increased rapidly in 2 weeks to 80.7 (1×MVA) and 125.3 (2×MVA), higher than after primary vaccination and comparable to boosted HSPX subjects. Six months after boosting, GMTs were 25.6 (1×MVA) and 49.3 (2×MVA). No safety concerns were identified. CONCLUSIONS: Anamnestic responses to boosting without sustained high nAb titers support presence of durable immunological memory following primary MVA-BN immunization. Clinical Trials Registration. NCT00316524 and NCT00686582.