Protective Antibody Titers Research Articles

Efficacy of live attenuated and inactivated bivalent vaccine against canine distemper and canine parvo viruses in dogs

Through the present work we succeeded to prepare live attenuated and inactivated canine distemper (CD) using Snyder Hill strain and canine parvo (CP) vaccines using CPV type 2a srain either in mono or bivalent formulae aiming to establish the most safe and potent vaccine formula that enable puppies to withstood both virus infections. It was found that monovalent and bivalent attenuated vaccines induced higher and longer duration of immunity, showed protective CD antibody titers (64-128 by SNT and 2.4log10 by ELISA) up to 12 months post vaccination while inactivated ones induced lower and shorter protective immune levels (32 by SNT and l.8 log10 by ELISA) for 10 months post vaccination. Also, CP antibody levels remained with high levels (64-128 by SNT and 2.5 by ELISA) up to 12 months as induced by attenuated mono and bivalent vaccine and with lower protective values (32-64 by SNT and 1.5- 1.9log10 by ELISA) by inactivated vaccines up to 11 months. Anyhow, it could be said that the bivalent CD and CP attenuated or inactivated vaccines can provide vaccinated puppies with specific protective antibodies against the two viruses.

Two Dose Series of High-Dose Influenza Vaccine Is Associated with Longer Duration of Serologic Immunity in Patients with Plasma Cell Disorders

Background:Patients with plasma cell disorders (PCDs) are highly susceptible to infections, including influenza, which are a major source of morbidity. Seasonal influenza vaccination is routinely administered to patients with PCDs, yet influenza infections remain common. Combining the use of higher antigen dose and a booster strategy, we recently reported a randomized study of a two dose series of high-dose influenza vaccine, which was associated with fewer influenza infections than standard influenza vaccination in patients with PCDs (Branagan, et al, ASH 2016). However, the immunologic effects following this vaccination strategy remains unknown. Few studies have focused on serologic responses to influenza vaccination in PCD patients and there are none to the authors' knowledge which have measured longitudinal serologic responses over a single flu season.Methods:We conducted a double-blind, randomized clinical trial over the 2015-16 flu season, comparing two doses of Fluzone® High-Dose influenza vaccination (separated by 30 days) to standard of care influenza vaccination. Patients were allocated to the experimental arm in 2:1 ratio. Standard of care influenza vaccination was considered single age-based vaccination (standard dose <65 years and high-dose ≥ 65 years) and patients in this arm received a saline placebo injection at 30 days to assist in blinding. Eligibility criteria allowed any patient with a plasma cell disorder and no contraindication to trivalent inactivated influenza vaccine. HAI titers were analyzed by standardized procedure at four time points, baseline, 30 days following the initial vaccine, 30 days following the second vaccine, and at the end of the flu season (April 30).Results:122 total plasma cell disorder patients were enrolled (97 with disease requiring therapy and 25 with asymptomatic gammopathy). Forty-eight patients received a single standard of care influenza vaccination and 74 patients received two doses of Fluzone High-Dose vaccine. Median age was 67 years (range 42-90). Following the second vaccine / placebo, rates of total seroprotection (against all 3 influenza vaccine strains) were 86.3% for patients who received two high dose vaccines and 63.9% for standard vaccination patients. At the end of the flu season, rates of total seroprotection were 58.5% for patients who received two high dose vaccines and 33.3% for standard vaccination patients. Chi-square testing revealed that patients receiving the two dose vaccine strategy experienced significantly higher rates of total seroprotection following second vaccine (p<0.05). At the end of the flu season rates of seroprotection trended toward significance at the end of the flu season against all 3 vaccine strains (p=0.07), against the H3N2 strain (p=0.05) and were significantly higher against the H1N1 strain (p<0.05).Conclusions:We previously reported that a two dose strategy of Fluzone® High-Dose influenza vaccine is safely tolerated in patients with plasma cell disorders and associated with fewer laboratory-confirmed influenza infections. Unexpectedly, the current analysis revealed that protective HAI antibody titers rapidly fall in PCD patients. Typically, HAI titers slowly decrease following a peak protective response, but do not drop below protective levels until after 6 months. However, PCD patients in this study began to lose HAI seroprotection within 4 months and even as little as 30 days. Interestingly, patients who received the two dose series of high-dose influenza vaccine maintained higher rates of seroprotection at the end of the influenza season compared to those who received standard vaccination. The maintenance of seroprotection was greatest against the seasonal H1N1 strain (which was the predominate circulating strain during that particular 2015-2016 flu season). Importantly, these results suggest that a two dose series of high-dose vaccine provides may mitigate loss of vaccine-induced HAI titers and allow more durable serologic protection throughout the flu season. Studies are ongoing to further explore immune function following influenza vaccination, including cell-mediated responses. More studies are warranted to help determine the optimal dose and timing of influenza vaccination in PCD patients. Understanding the unique kinetics of serologic responses in PCD patients may have practice changing implications for other vaccines and therapies in this population. DisclosuresNo relevant conflicts of interest to declare.

Efficacy of Early Post-Transplant Vaccination Using a Prime and Boost Strategy Is Independent of a Prior History of GvHD: Results from BMT CTN 0201

Introduction: BMT CTN 0201 was a randomized trial of bone marrow (BM) vs G-CSF mobilized peripheral blood (G-PB) grafts in 550 patients with leukemia or MDS undergoing allogeneic hematopoietic stem cell transplantation from unrelated donors. Responses to the 23-valent-pneumococcal vaccine are poor in elderly and immune-compromised patients, including allo-transplant recipients. A secondary objective of BMT CTN 0201 compared responses to post-transplant vaccination using protein-based diphtheria-tetanus (dT) vaccine followed by two doses of a diphtheria-pneumococcal polysaccharide conjugate (PCV7) and the 23-valent pneumococcal polysaccharide vaccine (PPV23).Methods: Vaccination started at 6 months post-transplant with dT followed by PCV7 at 7 and 9 months and PPV23 at 11 months post-transplant. Hepatitis B vaccination occurred at 6, 7 and 11 months. Serological responses in BMT CTN 0201 patients surviving to one year post-transplant were compared among those vaccinated per protocol (N=71), those that received partial vaccination (N=58) or no vaccines (N=39). Primary end-points were the fractions of vaccinated individuals with protective antibody titers to the 14 common pneumococcal bacterial serotypes, Hepatitis B, diphtheria and tetanus. Clinical history of acute or chronic GVHD, blood B-cells and T-cells, and serum immunoglobulin levels were studied as covariates of protective immunological responses.Results: Overall survival at 3 years across the cohorts that received full, partial, or no vaccination was similar (81%, 87%, 84%). Lack of compliance with protocol vaccination did not vary according to whether subjects had a history of acute or chronic GVHD. The frequency of patients with prior history of grade 2-4 acute GVHD or chronic GVHD were similar across the three cohorts (82%, 90%, 82%), with comparable rates of severe grades 3-4 acute (10%, 12%, 13%) and extensive chronic GVHD (63%, 67%, 64%, respectively). Serological responses to vaccines did not differ between recipients of BM vs G-PB grafts, or whether patients had a history of grade 2-4 acute GVHD or chronic GVHD. Serological responses were highly associated with protocol-specified vaccination, with median (range) of titers (ug/mL) for fully vaccinated versus non-vaccinated individuals for HepB: 10.81 (0.05-110) versus 0.49 (0.05-63) p=0.01; tetanus, 2.80 (0.16-20) versus 0.40 (0.05-20) p<0.001; diphtheria: 1.62 (0.05-20) versus 0.08 (0.05-1.2) p<0.001; as well as protective antibody titers to each of the component pneumococcal epitopes shared between PCV7 and PPV23 (Table 1, N=71 fully vaccinated and N=48 with no pneumococcal vaccines). Among the fully-vaccinated cohort, a greater proportion had protective antibodies to individual pneumococcal serotypes present in the PCV7 “prime” vaccine (median 66%) versus those restricted to the PPV23 “boost” vaccine (median 41%). Serum levels of IgA, IgM, and IgG at 12 months post-transplant were correlated with the kinetics of B-cell recovery in the blood at 3, 6, and 12 months. Antibody titers to tetanus, diphtheria and 8/14 of the tested pneumococcal serotypes were correlated with total serum IgG levels at 12 months post-transplant. Titers to diphtheria, a T-cell dependent antigen, were correlated with day +100 blood levels of T-cells, myeloid dendritic cells and B-cells (p<0.05), while antibody levels to serotypes in PCV7 were correlated with day +100 levels of B-cells in the blood.Conclusion: The efficacy of vaccination to specific pneumococcal serotypes among recipients of allogeneic transplants is enhanced by priming with dT and PCV7 prior to vaccination with the PPV23 vaccine. Vaccination is effective in patients with a history of acute or chronic GVHD. Strategies that enhance B-cell recovery post-transplant may improve responses to vaccines, especially those that are T-cell independent. [Display omitted] DisclosuresWaller:National Institutes of Health: Research Funding; Helocyte: Consultancy; Chimerix: Equity Ownership; Cerus: Equity Ownership; Coulter Foundation: Research Funding; PRA: Consultancy; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding; Cambium Medical Technologies: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Katz Foundation: Research Funding; AMGEN: Consultancy; Celldex: Consultancy.

Immunogenicity and Protective Efficacy of Iron-inactivated Pasteurella multocida A:1 Vaccine against Fowl Cholera in Backyard Chicken

Background: Fowl cholera is a highly fatal, contagious bacterial disease that incurs significant economic loss in commercial as well as back-yard poultry. Vaccination is the most effective way in controlling this disease. In this study, we prepared and evaluated the immunogenicity of iron- inactivated Pasteurella multocida A:1 vaccine and its protective efficacy against fowl cholera experimental infection in backyard chicken.Methods: Scaled up Pasteurella multocida A:1 culture with 5 X 108 CFU/ml equivalent to 2.5 mg of antigen per dose was used for preparation of experimental vaccines. Formalin inactivated and mixed with APS adjuvant (FIA), formalin inactivated-Freund adjuvant (FIF), Iron inactivated and adjuvanted with iron (III), Iron inactivated from iron supplemented media and adjuvanted with iron (ISII) and commercial oil emulsion vaccine (CV) were used in the study. A total of 120 Vanaraja birds (n=20/group) of 2 weeks age were immunized with these vaccine and booster were given at 3rd and 6th week with respective vaccine. Specific antibody titers were assessed by iELISA in the serum at weekly intervals. The birds were challenged (n=6 /group) with 5x104 CFU/ml of virulent isolate by intraperitoneal route and morbidity, mortality percentage were observed.Result: Protective antibody titers were induced by iron inactivated vaccine from 4th week of immunization and upon booster doses it induced significantly higher (P less than 0.05) antibody response. The iron inactivated experimental vaccine gave equivalent protection as that of commercial vaccine upon challenge infection.

Comparison of hemagglutination inhibition and hemagglutinin pseudovirus neutralization titres in relation to protection against influenza in a mouse model.

The hemagglutination inhibition (HI) test has long been used as a standard measure of antibody response for inactivated influenza vaccines. However, the HI test has limitations, such as insensitivity when using some H3N2 virus strains and failure to detect neutralizing antibodies that target regions distant from the receptor binding site. We therefore examined a hemagglutinin pseudovirus neutralization (PVN) test as a possible supplement or alternative to the HI test. We evaluated the association of HI or PVN titres with protection against influenza infection in mice based on morbidity (where the illness was defined as 25% body weight loss). We assessed this relationship using dose-response models incorporating HI or PVN titres as a variable. The morbidity was correlated with the pre-exposure titres, and such a correlation was well described by a modified dose-response model. The mathematical modelling suggests that PVN titres consistently show a stronger association with invivo protection as compared to HI titres in mice. Given our findings, the PVN test warrants further investigation as a tool for evaluating antibody responses to influenza vaccines containing hemagglutinin. The resulting models may also be useful for analyzing human clinical data to identify potentially protective antibody titres against influenza illness.

Sustainability of neutralising antibodies induced by bivalent or quadrivalent HPV vaccines and correlation with efficacy: a combined follow-up analysis of data from two randomised, double-blind, multicentre, phase 3 trials

Quadrivalent and bivalent vaccines against oncogenic human papillomavirus (HPV) are used worldwide with different reported overall efficacies against HPV infections. Although protective concentrations of vaccine-induced antibodies are still not formally defined, we evaluated the sustainability of neutralising antibodies in vaccine trial participants 2-12 years after vaccination and the correlation with reported vaccine efficacy. We did a follow-up analysis of data from the Finnish cohorts of two international, randomised, double-blind, phase 3 trials of HPV vaccines, PATRICIA (bivalent, HPV16 and 18) and FUTURE II (quadrivalent, HPV6, 11, 16, and 18). In 2002 and 2004-05, respectively, Finnish girls aged 16-17 years participated in one of these two trials and consented to health registry follow-up with the Finnish Cancer Registry. The cohorts were also linked with the Finnish Maternity Cohort (FMC) that collects first-trimester serum samples from nearly all pregnant Finnish women, resulting in 2046 post-vaccination serum samples obtained during up to 12 years of follow-up. We obtained serum samples from the FMC-based follow-up of the FUTURE II trial (from the quadrivalent vaccine recipients) and the PATRICIA trial (from corresponding bivalent vaccine recipients who were aligned by follow-up time, and matched by the number of pregnancies). We assessed neutralising antibody concentrations (type-specific seroprevalence) to HPV6, 16, and 18, and cross-neutralising antibody responses to non-vaccine HPV types 31, 33, 45, 52, and 58 from 2 to 12 years after vaccination. Up to Dec 31, 2016, we obtained and analysed 577 serum samples from the quadrivalent vaccine recipients and 568 from the bivalent vaccine recipients. In 681 first-pregnancy serum samples, neutralising antibodies to HPV6, 16, and 18 were generally found up to 12 years after vaccination. However, 51 (15%) of 339 quadrivalent vaccine recipients had no detectable HPV18 neutralising antibodies 2-12 years after vaccination, whereas all 342 corresponding bivalent vaccine recipients had HPV18 neutralising antibodies.. In seropositive quadrivalent vaccine recipients, HPV16 geometric mean titres (GMT) halved by years 5-7 (GMT 3679, 95% CI 2377 to 4708) compared with years 2-4 (6642, 2371 to 13 717). Between 5 and 12 years after vaccination, GMT of neutralising antibodies to HPV16 and 18 were 5·7 times and 12·4 times higher, respectively, in seropositive bivalent vaccine recipients than in the quadrivalent vaccine recipients. Cross-neutralising antibodies to HPV31, 33, 45, 52, and 58 were more prevalent in the bivalent vaccine recipients but, when measurable, sustainable up to 12 years after vaccination with similar GMTs in both vaccine cohorts. Seroprevalence for HPV16, 31, 33, 52, and 58 significantly correlated with vaccine efficacy against persistent HPV infections in the bivalent vaccine recipients only (rs=0·90, 95% CI 0·09 to 0·99, p=0·037, compared with rs=0·62, 95% CI -0·58 to 0·97, p=0·27 for the quadrivalent vaccine recipients). Correlation of protection with prevalence of neutralising or cross-neutralising HPV antibodies was not significant in the quadrivalent vaccine recipients. The observed significant differences in the immunogenicity of the two vaccines are in line with the differences in their cross-protective efficacy. Protective HPV vaccine-induced antibody titres can be detected up to 12 years after vaccination. Academy of Finland and Finnish Cancer Foundation.

Elimination of cervical cancer depends on HPV vaccination and primary HPV screening

WHO has put forth a challenge for the next century to reduce the incidence of cervical cancer globally to fewer than four cases per 100 000 women, a level equated with elimination. 1 WHOTo eliminate cervical cancer in the next 100 years, implementing an effective strategy is critical. https://www.who.int/news/item/04-02-2020-to-eliminate-cervical-cancer-in-the-next-100-yearsDate accessed: May 15, 2021 Google Scholar Globally, the range of cervical cancer incidence is far from the WHO goal, with one of the lowest human development index (HDI) countries Eswatini at 75·3 cases per 100 000 women, 2 Arbyn M Weiderpass E Bruni L et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health. 2020; 8: e191-e203 Summary Full Text Full Text PDF PubMed Scopus (1118) Google Scholar and the higher HDI regions at 10·4 cases per 100 000 women. 3 Bray F Ferlay J Soerjomataram I Siegel RL Torre LA Jemal A Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68: 394-424 Crossref PubMed Scopus (45408) Google Scholar Historically, cervical cancer incidence has steadily decreased because of opportunistic and organised screening programmes. Between 1990 and 1995, Finland reached a cervical cancer incidence of fewer than four cases per 100 000 women through organised screening; nonetheless, a subsequent decrease in participation in screening among women aged 30–35 years led to an increased incidence within a 5-year timeframe. 4 Harper DM Nieminen P Paavonen J Lehtinen M Cervical cancer incidence can increase despite HPV vaccination. Lancet Infect Dis. 2010; 10: 594-595 Summary Full Text Full Text PDF PubMed Scopus (31) Google Scholar Cytology as a primary screen has been replaced by primary human papillomavirus (HPV) cervical screening, which has a 70% greater protection against invasive cervical cancer than cytology. 5 Ronco G Dillner J Elfström KM et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014; 383: 524-532 Summary Full Text Full Text PDF PubMed Scopus (1020) Google Scholar Sustainability of neutralising antibodies induced by bivalent or quadrivalent HPV vaccines and correlation with efficacy: a combined follow-up analysis of data from two randomised, double-blind, multicentre, phase 3 trialsThe observed significant differences in the immunogenicity of the two vaccines are in line with the differences in their cross-protective efficacy. Protective HPV vaccine-induced antibody titres can be detected up to 12 years after vaccination. Full-Text PDF

Long -term persistence of antibodies against varicella in fully immunized healthcare workers: an Italian retrospective cohort study

BackgroundChickenpox is a highly contagious disease caused by the varicella zoster virus (VZV), and in infants, adolescents, adults, pregnant women, and the immunocompromised it can be serious. The best way to prevent chickenpox is immunization with the varicella vaccine. Protective levels of antibodies induced by the varicella vaccine decline over time, but there is currently no formal recommendation for testing anti-varicella zoster virus (VZV) IgG levels in immunized healthcare workers (HCWs).MethodsThe aims of this study were to evaluate the seroprevalence of circulating anti-VZV IgG in a sample a sample of students and residents of the medical school of the University of Bari, the long-term immunogenicity of the varicella vaccine, and the effectiveness of a strategy consisting of a third vaccine booster dose. The study population was screened as part of a biological risk assessment conducted between April 2014 and October 2020. A strategy for the management of non-responders was also examined.ResultsThe 182 students and residents included in the study had a documented history of immunization (two doses of varicella vaccine). The absence of anti-VZV IgG was determined in 34% (62/182; 95%CI = 27.2–41.4%), with serosusceptibility more common among males than females (p < 0.05). After a third varicella dose, seroconversion was achieved in 100% of this previously seronegative group. No serious adverse events were recorded.ConclusionsOne-third of the study population immunized against VZV lacked a protective antibody titer, but a third dose of vaccine restored protection. Since it is highly unlikely that VZV will be eliminated in the immediate future, the loss of immunity in a substantial portion of the population implies a risk of varicella outbreaks in the coming years. Screening for varicella immunity in routine assessments of the biological risk of medical students and HCWs may help to prevent nosocomial VZV infections.

Oral Proteasome Inhibitor Ixazomib for Switch-Maintenance Prophylaxis of Recurrent or Late Acute and Chronic Graft-versus-Host Disease after Day 100 in Allogeneic Stem Cell Transplantation

Graft-versus-host disease (GVHD) is a frequent complication in the first year after allogeneic stem cell transplantation (allo-HCT). Recipients of reduced-intensity (RI) or nonmyeloablative (NMA) conditioning combined with calcineurin inhibitor (CNI)-based GVHD prophylaxis frequently develop GVHD in the context of immunosuppression taper. Ixazomib is an oral proteasome inhibitor with a wide safety profile that has demonstrated immunomodulatory properties, inhibition of pro-inflammatory cytokines, and anti-tumor activity. We hypothesized that switch-maintenance GVHD prophylaxis using ixazomib would facilitate CNI taper without increased GVHD frequency and severity while maintaining graft-versus-tumor (GVT) effect and an acceptable safety profile. We conducted an open-label, prospective, single-center pilot study in patients with hematologic malignancies who received an RI or NMA conditioning and CNI-based GVHD prophylaxis that were within day 100 to 150 after HCT (n=18). Patients were treated with ixazomib once weekly on a 28-day cycle (3 weeks on, 1 week off). Treatment was safe; most adverse events were grade 1 or 2, with cytopenia and elevation in transaminases the most common. Five patients were removed from the study because of toxicity or side effects. Only 5 of 18 patients developed GVHD during the study, and its severity was driven by acute manifestations while chronic involvement was mild. The cumulative incidence of grade II-IV acute and chronic GVHD at 1-year after HCT was 33% (95% confidence interval [CI], 13-55). No patients died during the study, and only 1 had malignant relapse. An additional patient relapsed after completion of the study but within 1 year after HCT. The probability of progression-free survival and GVHD-free/relapse-free survival (composite endpoint) at 1 year were 89% (95% CI, 75-100) and 78% (95% CI, 61-100), respectively. Immune reconstitution analysis showed a rapid and sustained recovery in T-cell subpopulations and B cell reconstitution, and vaccine response in a subset of patients demonstrated continuing or de novo positive protective antibody titers. This study demonstrated low incidence of recurrent and late acute and chronic GVHD within 1 year after HCT possible associated with switch-maintenance GVHD prophylaxis using ixazomib. This approach allowed for CNI taper while preserving GVT effect, without aggravating GVHD. Our findings support further development of this approach and provide a proof-of-concept for switch-maintenance GVHD prophylaxis.

English

BACKGROUND Hepatitis B virus (HBV) has long been recognized as a work-related hazard for health-care personnel (HCP). HCPs are all paid and unpaid persons giving health care or working or training in health-care settings, who have reasonably expected risks for exposure to infectious materials. Post-vaccination serological testing is suggested 4 to 8 weeks after completion of the primary course in all health care workers. If the anti - HBs levels are less than 10 mIU / ml 4 - 8 weeks after the third dose of vaccine, the person's serum has to be tested for markers of HBV. The objective of the study was to evaluate the immune response after hepatitis B vaccination in health care workers. METHODS This study was a cross-sectional study that was conducted for a period of one year (January 2016 – December 2016). In this study, blood samples of 211 HCP were collected and sera were tested for quantitative anti - HBs level using anti - HBs EIA kit (Diapro, Italy). RESULTS 75. 83 % of HCP were completely vaccinated and 24.17 % did not complete the three-dose regimen. 91.87 % of completely vaccinated HCP had an anti- HBs titre of more than 10mIU/ml while 80.39 % of incompletely vaccinated HCP had protective antibody levels. 71.42 % of males and 90.35 % of females had protective antibody titre. The housekeeping staff were the most protected (100 %) while doctors were the least protected (54.54 %). Among the different vaccine, compliant subgroups 85.96 % of HCP who were completely vaccinated and had not taken booster dose had protective antibody titre even after five years where as 90.47 % of HCP who were completely vaccinated and had taken a booster dose and had protective antibody titre even after 5 years. It was also noted that 95.23 % of HCP who were vaccinated before the age of 20 had a protective antibody titre while only 70.58 % of those who got vaccinated after the age of forty had a protective antibody titre. CONCLUSIONS The records, if possible retrievable electronic records, should be maintained in health care centers as a reference in case of occupational exposure or for other purposes. KEYWORDS Hepatitis B, Anti HBs, Health Care Personnel

Serosurveillance of rabies antibodies in dogs in Mumbai region by using indirect ELISA

Rabies is a highly fatal viral infection of the central nervous system affecting all warm-blooded animals including humans. To implement the preventive and control measures, it is important to decide the status of anti-rabies antibodies in dogs. Out of 120 serum samples, 47 (39.2 %) serum samples, showed an antibody titre equal to or above the cut off value of 0.5 IU/ml. The maximum number of dogs showed anti-rabies antibody titres equal to or above the cut-off value of 0.5 IU/ml after <1 month pre-exposure to the rabies vaccine. In 15 serum samples of pet dogs, we observed 13 (86.66 %) dogs with protective anti-rabies antibody titre. Statistical analysis suggests that the age of the animal had no significant effect on anti-rabies antibody titre in vaccinated pet dogs. The overall low seroprevalence of anti-rabies antibody in stray dogs indicates their susceptibility to rabies infection and thus posing a risk of rabies to other animals and humans.

The dynamics and association of B and T cell receptor repertoires upon antibody response to hepatitis B vaccination in healthy adults

ABSTRACT The Hepatitis B (HB) vaccine is efficacious in preventing hepatitis B virus infection. However, the association between antibody response to the HB vaccine and dynamic immune repertoire changes in different cell subsets remains unclear. Nine healthy participants were administered three doses of HB vaccine following the 0, 1, 6 month schedule. Peripheral CD4+ T, memory B (MB), naïve B (NB), and plasma cells (PCs) were sorted before vaccination and 7 days following each dose. The complementary determining region 3 of T-cell receptor β (TCRβ) chain and B-cell receptor (BCR) heavy chain (IgG, IgM, IgA) repertoires were analyzed by high-throughput sequencing. All nine participants elicited protective antibody titers to the vaccine at the end of immunization. Compared with the baseline, MB cells showed a significant increase in IgG usage and decreased IgM usage and repertoire diversity at the end of vaccination. TCRβ diversity changes were highly correlated with those of the BCR in MB cells in participants with a faster and robust antibody responses. The percentage of shared clonotypes between NB and MB cells, and MB cells and PCs were much higher than that between NB cells and PCs. The more clonotypes sharing the faster and stronger antibody responses were observed after HB vaccination. These results suggest the integral involvement of MB cells in vaccine immunization. Interaction between CD4+ T and MB cells and B cell differentiation may improve antibody response to HB vaccine.

Are patients with rheumatic diseases on immunosuppressive therapies protected against preventable infections? A cross-sectional cohort study

ObjectiveTo evaluate the prevalence of infections, prevalence of hospitalisation due to infections, the vaccination status and perceived screening of infections prior to the start of biologic disease modifying antirheumatic drugs...

Circulating Tfh cell and subsets distribution are associated with low\u2010responsiveness to hepatitis B vaccination

BackgroundAn estimated 5–10 % of healthy vaccinees lack adequate antibody response following receipt of a standard three-dose hepatitis B vaccination regimen. The cellular mechanisms responsible for poor immunological responses to hepatitis B vaccine have not been fully elucidated to date.MethodsThere were 61 low responders and 56 hyper responders involved in our study. Peripheral blood samples were mainly collected at D7, D14 and D28 after revaccinated with a further dose of 20 µg of recombinant hepatitis B vaccine.ResultsWe found low responders to the hepatitis B vaccine presented lower frequencies of circulating follicular helper T (cTfh) cells, plasmablasts and a profound skewing away from cTfh2 and cTfh17 cells both toward cTfh1 cells. Importantly, the skewing of Tfh cell subsets correlated with IL-21 and protective antibody titers. Based on the key role of microRNAs involved in Tfh cell differentiation, we revealed miR-19b-1 and miR-92a-1 correlated with the cTfh cell subsets distribution and antibody production.ConclusionsOur findings highlighted a decrease in cTfh cells and specific subset skewing contribute to reduced antibody responses in low responders.

Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort

IntroductionIn light of the SARS-CoV-2 pandemic, protecting vulnerable groups has become a high priority. Persons at risk of severe disease, for example, those receiving immunosuppressive therapies for chronic inflammatory cdiseases...

Immunological Protection of Individuals Aged 3 to 25 Years Against Pertussis: Regional Cross-Sectional Study

Background. Recently, there has been an increase in the incidence of pertussis in unvaccinated, as well as vaccinated children and adults. The major risk group for pertussis are infants and children over 4 years of age due to gradual decrease in basic immunity. Objective. The aim of the study was to analyze postvaccinal immunity against pertussis in individuals aged 3 to 25 years in Krasnodar. Methods. The study was carried out in the period between July 2018 and October 2019 and included patients aged 3 to 25 years with completed (according to National Immunization Schedule) immunization against pertussis with no history of pertussis in the past. Postvaccinal immunity against pertussis in this sample was determined by the ratio of study participants with minimum protective antibodies titer to Bordetella pertussis (≥ 1:160). Results. The minimum protective antibody titer was revealed in 24 out of 76 participants. Distribution to age groups was the following: children aged 3 to 7 years — 2/28 (7%), 8 to 17 years — 13/22 (59%; p &lt; 0.001, compared with the younger age group), ≥ 18 years — 9/26 (35%; p = 0.017). There was no postvaccinal immunity (no antibodies detected) in 6 (21%), 1 (5%) and 4 (15%) participants, respectively. Conclusion. Insufficient postvaccinal (humoral) immunity against pertussis was revealed in majority of children under 7 years. The ratio of such children decreases with age. It suggests the presence of hidden circulation of Bordetella pertussis and, as a result, previous medical condition in erased or abortive form.

Safety and immunogenicity of rabies vaccine as 4 - dose Essen Intramuscular regimen for post exposure prophylaxis: A non - randomized, comparative controlled study

ABSTRACT Introduction: World Health Organization has recommended that in healthy persons with category III exposures, who receive wound care and rabies immunoglobulin infiltration, a vaccine regimen consisting of 4 doses administered intramuscularly on days 0, 3, 7, and 14 can be used as an alternative to the 5-dose intramuscular regimen. Objective: To assess the clinical safety and immunogenicity of rabies vaccine administered as 4-dose Essen intramuscular regimen for post-exposure prophylaxis. Methods: A non-randomized, comparative, controlled study was conducted at the anti-rabies clinic, KIMS Hospital and Research Center, Bangalore, India. The study subjects were divided into study group i.e., 4-dose intramuscular regimen, and control group i.e., 5-dose intramuscular regimen, and were given post-exposure prophylaxis. All subjects were followed for any adverse drug events. Rabies virus neutralizing antibodies was determined on day 14, 90 & 180 at the WHO collaborating center, NIMHANS, Bangalore, India to assess the immunogenicity. Results: The present study included 70 adult animal bite victims, 35 each in study group and control group. The incidence of ADEs was 7.8% in 4-dose Essen group and 7.0% in 5-dose Essen group;the difference between them was not significant (P > .05). Similarly, all the subjects in both the groups had protective antibody titers of ≥ 0.5 IU/mL (100% seroprotective) from day 14 till day 180; the difference between two groups was also not significant (P > .05). Conclusion: The 4-dose intramuscular Essen post-exposure prophylaxis regimen was found to be clinically safe and immunogenic.

Prototype Pentavalent Bovine Leptospira Vaccines Blended with Oil Adjuvant Provides Protection and Prevents Renal Colonization in Guinea Pig Model

Background: Leptospirosis significantly impacts the economy of livestock farmers by causing reproductive failure and production losses in bovines. The control of bovine leptospirosis requires a combination of vaccination programme, biosecurity measures and chemotherapeutic regimens. Vaccination protect the clinical diseases and reduces/prevents renal colonisation of Leptospires and in turn reduces excretion of leptospires in urine which is a major source of environmental contamination. Some serovars of leptospires require cell mediated immunity apart from humoral immunity. This study was undertaken to develop prototype vaccine with prevalent serogroups to induce humoral and cell mediated immunity. Immunogenicity of the prototype vaccines and their safety were assessed experimentally in Guinea pigs.Methods: An inactivated oil adjuvant prototype pentavalent bovine leptospira vaccines with serogroups Australis, Hebdomadis, Hardjo, Javanica and Pomona which were prevalent in Tamil Nadu were developed and compared with the aluminium hydroxide gel adjuvant vaccine. The humoral immune response was assessed measuring antibodies by Microscopic Agglutination Test and Cell Mediated Immune response was assessed by lymphocyte proliferation assay. The ability of these vaccines to protect Guinea pigs against virulent Leptospires challenge was also demonstrated.Result: The prototype vaccine blended with oil adjuvants resulted in higher protective antibody titres of more than 6.64 log2 (≥1:100) than the aluminium hydroxide adjuvant blended vaccine. The protective antibody titres lasted upto 180 days, except for serogroup Javanica (150 days). The Montanide adjuvants were able to produce cell mediated immune response for protection against serovar Hardjo. Challenge study in guinea pigs showed complete protection following vaccination using pentavalent vaccine blended with Montanide adjuvants, while the aluminium hydroxide adjuvant was able to confer only partial protection. The Montanide blended prototype vaccines were also able to prevent renal colonisation of all five serogroups. This study shows the potential of the oil adjuvant blended multivalent vaccine for use in vaccination programmes against bovine leptospirosis.

Health screening for new entry medical students at Newcastle University Medicine (NUMed) Malaysia: a 4-year cross-sectional study

Background Newcastle University Medicine (NUMed) Malaysia adheres to the UK Medical Schools protocol on screening for blood borne viruses including hepatitis B (HBV), Hepatitis C and HIV as health requirements for new entry medical students’ admissions and continuing medical practice. This study specifically aims to assess the outcome of HBV vaccination and the subsequent seroconversion status along with other required vaccinations. Methods This 4-year cross-sectional study included 345 new entry Malaysian medical students to NUMed from 2015 to 2018 excluding 80 students with missing data. Demographic data, HBV vaccination status, and HBV surface antibody (anti-HBs) titers were obtained from participants’ health screening reports and recorded in a pre-designed data template. Seroconversion status (anti-HBs titer &gt;10 IU/L) measured using an enzyme-linked immunoassay, was determined and seroconversion rates were calculated. None of the participants received a booster anytime prior to testing. Both demographic and vaccination data were matched to investigate seroconversion rate in relation to ethnicity and gender. Chi-square test was used for analysis using Prism with statistical significance defined as P &lt; 0.05. Results Out of 345, only 223 (64.6%) vaccinated individuals showed seroconversion, while 117 (33.9%) did not seroconvert. Among participants, 121 (35.1%) were male and 224 (64.9%) were female. The majority of the participants were of Chinese ethnicity (62.0%), followed by Malay (19.7%) and Indian ethnicity (18.3%). None of the 345 new entry medical students were tested positive for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc), indicating an overall HBV prevalence of 0%. A total of 287 participants (83.2%) were vaccinated against varicella-zoster virus, while 58 (16.8%) were not vaccinated. Vaccination coverage of other vaccines, such as measles, rubella, MenQ and yellow fever were 257 (74.5%), 237 (68.7%), 154 (44.6%) and 20 (5.8%) respectively. There is no significant difference in the seroconversion rate of HBV vaccine between male participants (62.0%) and female participants (64.3%, P = 0.298). However, there is a statistically significant difference in the HBV seroconversion rate between the 3 ethnicity groups, with students of Malay ethnicity showing the lowest seroconversion rate of 47.1%, followed by those of Indian (68.3%) and Chinese ethnicity (69.6%) (P = 0.002). Conclusions This is the first study demonstrating a low HBV vaccine seroconversion rate (64.6%) among young new entry medical students at NUMed (median age: 19) following standard recommended 3-dose vaccination. Students of Malay ethnicity showed a significant non-conversion rate of 51.5% (p=0.002) as compared to the students of Chinese (29.4%) and Indian (28.6%) origin. Previous studies showed seroconversion rates of over 90% and further studies should be considered to investigate why this young population of Malaysian students did not mount protective antibody titer.

Tolerance and humoral immune response to the yellow fever vaccine in sickle cell disease children treated with hydroxyurea: a multicentre prospective study

Sickle Cell Disease (SCD) children are frequent travellers to countries where Yellow Fever (YF) is endemic, but there are no data regarding the safety and immunogenicity of the vaccine in such children treated with hydroxyurea (HU). The main objective of this study was to compare the tolerance and immune response to YF vaccination in SCD children treated or not with HU. SCD Children < 18years attending the international travel clinics of three large paediatric centres and requiring a first YF vaccination were included in a prospective study. Adverse events were collected 2weeks after vaccination. YF vaccine antibody titres were measured approximately 6months after vaccination. Among the 52 SCD children vaccinated against YF, 17 (33%) were treated with HU. Only mild adverse events, mainly fever and local reaction, were observed in the HU group with a similar frequency in the non-HU group (57% and 35%, respectively, p = 0.30). YF antibody titres were measured in 15/17 patients in the HU group and 23/35 patients in the non-HU group after a median of 6.0months (3.5-8.5) following vaccination. The geometric mean of YF antibody titre was similar in both groups. A protective antibody level was observed in 85% of the children in the HU group versus 100% in the non-HU group (p = 0.14), suggesting a lower effectiveness of the vaccine in patients on HU similarly to what has been described in patients on immune suppressive therapy for other vaccines. YF vaccination seems to be safe and efficient in SCD children treated with HU. Considering the potential risk of severe complications in cases of YF while travelling in Africa for those patients, the benefit-to-risk ratio argues for YF vaccination in all SCD children. Control of a protective antibody titre may also be useful to ascertain an adequate response in those treated with HU.