Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals,a prospective longitudinal cohort study

PurposeAs protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion.MethodsA prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster.ResultsAmong 110 participants, 56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25–11.67) folds and 2.40 (95 %CI 1.90–3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5–79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1–34.7) fold in and immunocompetent group, was observed.ConclusionA third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.     

Immunogenicity after pre- and post-exposure rabies vaccination: A systematic review and dose-response meta-analysis

BackgroundThere are a myriad of vaccine schedules for rabies pre- (PrEP) and post-exposure prophylaxis (PEP) that differ in the number and time doses, number of visits, length of schedule, and route of administration. The objective of this study was to systematically review the evidence and investigate how the differences in schedules influence titres over time.MethodsFour databases were searched from inception to January 2020 for rabies PrEP and PEP studies. A dose–response meta-analysis was utilised to pool geometric mean titres (GMT) over time. Subgroup analyses by route of administration, age group, and schedule were conducted.Results80 studies met the inclusion criteria and contributed with 191 datasets and 12,413 participants. Both intradermal (ID) and intramuscular (IM) PrEP/PEP produce adequate GMTs. Significantly lower GMT levels were achieved in older (>50yrs) compared to younger (<50yrs) participants. Short 1-week schedules were as effective as longer schedules that can take between 3 and 12 weeks to complete.ConclusionsSeveral effective ID and IM schedules were identified, the selection of a schedule should take into account the patient’s needs, costs, availability to return for subsequent doses, and the time required to complete the schedule. Older individuals warrant special attention as they develop lower antibody response.     

Immunogenicity and safety of two-visit,intradermal pre-exposure rabies prophylaxis simultaneously administrated with chimeric live-attenuated Japanese encephalitis vaccine in children living in rabies and Japanese encephalitis endemic country

BackgroundReducing the number of doses required for pre-exposure prophylaxis (PrEP) would make it more feasible and cost-effective to implement in children at the highest risk of rabies exposure in Asia. We studied immune response of 2-site intradermal (ID) injection of rabies vaccine on days 0 and 28 for rabies PrEP simultaneously administrated with live-attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) for children living in endemic area.Research design and methodsSeronegative children (n = 49) aged 12–16 months were randomized 2:1 into two groups: Group A subjects were vaccinated with 0.1-mL ID injection of purified Vero cell rabies vaccine (PVRV), each at two sites on day (D) 0 and D28; Group B subjects were vaccinated with conventional 0.5-mL intramuscular PVRV on D0, D7 and D28. Both groups received one dose of JE-CV subcutaneously on D0 and D365. Rabies virus neutralizing antibody (RVNA) titers were measured on D0, D42 and D365 after vaccination; Japanese Encephalitis (JE) neutralizing antibody titers were determined on D0, D42, D365 and D379.ResultsAll children had RVNA ≥ 0.5 IU/mL on D42 (geometric mean titers [GMTs] of RVNA 14.35 IU/mL [Group A] and 14.83 IU/mL [Group B], p > 0.05]). On D365, RVNA GMTs of subjects in group A and B were 1.50 IU/mL and 2.00 IU/mL (p > 0.05), respectively. All children had seroprotection following booster dose of JE-CV. There were no vaccine-related SAEs observed.ConclusionThe 2-site ID PrEP with PVRV on days 0 and 28 co-administrated with JE-CV are safe and immunogenic.     

Cost-effectiveness of rabies post-exposure prophylaxis in the context of very low rabies risk: A decision-tree model based on the experience of France

IntroductionBenefit-risk of different anti-rabies post-exposure prophylaxis (PEP) strategies after scratches or bites from dogs with unknown rabies status is unknown in very low rabies risk settings.Design and settingA cost-effectiveness analysis in metropolitan France using a decision-tree model and input data from 2001 to 2011.PopulationA cohort of 2807 patients, based on the mean annual number of patients exposed to category CII (minor scratches) or CIII (transdermal bite) dog attacks in metropolitan France between 2001 and 2011.InterventionsFive PEP strategies: (A) no PEP for CII and CIII; (B) vaccine only for CIII; (C) vaccine for CII and CIII; (D) vaccine+ rabies immunoglobulin (RIG) only for CIII; and (E) vaccine for CII and vaccine+ RIG for CIII.Main outcomes measuresThe number of deaths related to rabies and to traffic accidents on the way to anti-rabies centers (ARC), effectiveness in terms of years of life gained by reducing rabies cases and avoiding traffic accidents, costs, and incremental cost-effectiveness ratios (ICER) associated with each strategy.ResultsStrategy E led to the fewest rabies cases (3.6 × 10⁻⁸) and the highest costs (€1,606,000) but also to 1.7 × 10⁻³ lethal traffic accidents. Strategy A was associated with the most rabies cases (4.8 × 10⁻⁶), but the risk of traffic accidents and costs were null; therefore, strategy A was the most effective and the least costly. The sensitivity analysis showed that, when the probability that a given dog is rabid a given day (P_A) was >1.4 × 10⁻⁶, strategy D was more effective than strategy A; strategy B became cost-effective (i.e. ICER vs strategy A <3 × French Gross Domestic Product per capita) when P_A was > 1.4 × 10⁻⁴.ConclusionsIn the metropolitan France's very low rabies prevalence context, PEP with rabies vaccine, administered alone or with RIG, is associated with significant and unnecessary costs and unfavourable benefit-risk ratios regardless to exposure category.     

Single-visit, 4-site intradermal (ID) rabies vaccination induces robust immune responses 5 years after 1-week, 4-site ID primary post-exposure prophylaxis in the Philippines

BackgroundIn a randomized controlled study (NCT01622062) a 1-week, 4-site intradermal (ID, 4-4-4-0-0) post-exposure prophylaxis (PEP) rabies vaccination regimen with purified Vero cell rabies vaccine (PVRV, Verorab®, Sanofi Pasteur), either without (Group 1) or with (Group 2) purified equine rabies immunoglobulin (ERIG), patients in the Philippines achieved seroconversion rates at Day 14 that were non-inferior to that of the updated Thai Red Cross (TRC) 28-day, 2-site (2-2-2-0-2) ID regimen with ERIG (Group 3). Presented here are the annual immunogenicity data up to five years after the last primary dose, and the immunogenicity and safety data following simulated PEP with single-visit, 4-site ID regimen.MethodsRabies virus neutralizing antibodies (RVNA) were determined by rapid fluorescent focus inhibition test (RFFIT). Participants (n = 397) received simulated PEP vaccination ID at Year 5 and RVNAs were assessed at Day 11 post-vaccination.ResultsSeroconversion rates (RVNA titres ≥ 0.5 IU/mL) during annual follow-up remained >95% in Group 1 and were relatively stable at 80–90% in Group 2, but decreased from 80% to 64% in Group 3. RVNA geometric mean titres (GMTs) in Group 1 were consistently higher than in the other two groups, and those in Group 3 were generally lower than in the other two groups. There was a clear anamnestic response to vaccination in all groups, with all participants achieving RVNA titres ≥ 0.5 IU/mL at Day 11 post-simulated PEP booster vaccination. There were no safety concerns raised during annual follow-up and with simulated post-exposure vaccination with PVRV.ConclusionThe shortened, 1-week, 4-site ID regimen with PVRV achieved persistently higher RVNA titres than the updated 2-site TRC regimen, and more participants remained seroprotected up to five years after the last dose of primary immunization. Simulated post-exposure with 4-site ID rapidly induced an anamnestic response indicative of robust protection.     

Neutralizing antibody response after intradermal rabies vaccination in hemodialysis patients

Abnormal immune function in chronic hemodialysis (HD) patients could impair immunologic responsiveness to various vaccinations. Such inadequate response makes the HD patients to be at risk of certain fatal but preventable diseases including rabies. Although the effectiveness of rabies vaccination has been established in healthy subjects, the responsiveness of the current rabies vaccination has never been examined in HD patients. The effectiveness of post-exposure rabies vaccine was assessed in 20 stable thrice-a-week chronic HD patients who received adequate dialysis and did not have history of rabies vaccination during the last 20 years. All participants received the standard intradermal Thai Red Cross post-exposure rabies vaccination. Blood samples were obtained for determination of rabies neutralizing antibody (Nab) before the first dose (day 0) and on days 14 and 90 after vaccination. Prior to simulated vaccination, six of twenty patients already had Nab titers above the protective levels of 0.5 IU/mL while the remaining fourteen patients showed undetectable Nab. All subjects reached Nab titers above 0.5 IU/mL(acceptable level for rabies protection) by days 14 after vaccination. The geometric mean titers (GMTs) on days 14 after vaccination were 3.2 + 3.1 IU/mL (range 0.81–9.17 IU/mL). At day 90 after vaccination, 13 of 14 patients had Nab titers above the protective levels, resulting in the response rate of 92.8%. The GMTs of Nab on day 90 after vaccination were 5.09 + 1.79 IU/mL (0.42–25.0 IU/mL). There were no correlations between Nab titers and patient characteristics. No serious adverse reactions were detected. In conclusion, chronic HD patients receiving adequate dialysis have excellent protective immunological response after intradermal post-exposure rabies vaccination as WHO recommendation.     

Incidence and variables associated with inadequate antibody titers after pre-exposure rabies vaccination among veterinary medical students

Background

This study sought to determine the proportion of subjects with inadequate antibody titers at two years after pre-exposure rabies vaccination and identify variables associated with inadequate antibody titers.

Methods

A retrospective chart review of vaccination records of veterinary students in Michigan, 2004–2009, was conducted. Antibody titers <0.5 IU/ml as estimated by rapid fluorescent focus inhibition test were classified as inadequate. Variables were compared between the two groups to identify factors associated with inadequate titers at two years.

Results

A total of 603 subjects (mean age 24.1 ± 4.2 years, male:female 106:497) were included. Nearly one third (177/603, 29.4%) had inadequate titers at two years. Male gender (adjusted odds ratio (AOR) 1.87, 1.07–3.27; p = 0.029), vaccine manufacturer (AOR 1.49, 1.16–1.92; p = 0.002), BMI >25 (AOR 1.61, 1.02–2.54; p = 0.043), and duration between first and third doses of vaccine >21 days (AOR 2.49, 1.26–4.97; p = 0.009) were independently associated with inadequate titers.

Conclusions

Twenty-nine percent of subjects had inadequate antibody titers against rabies at 2 years. Gender, vaccine type/manufacturer, BMI of 25 or greater, and more than 21 days between the first and third doses of vaccine were independently associated with inadequate antibody titers at two years. Our data would support modifying the recommendations, so the third dose is recommended at 21 days rather than 21–28 days.     

Estimated protective effectiveness of intramuscular immune serum globulin post-exposure prophylaxis during a measles outbreak in British Columbia,Canada, 2014

IntroductionIntramuscular Immune Serum Globulin (IM ISG) is recommended as post-measles exposure prophylaxis (PEP) when administered within 6 days of initial exposure, with variable effectiveness in preventing measles disease. Effectiveness of IM ISG PEP in preventing clinical measles was assessed during a 2014 measles outbreak among a religious-affiliated community in British Columbia, Canada.Material and methodsFifty-five self-reporting measles susceptible contacts were offered exclusively IM ISG PEP within an eligibility period best surmised to be within 6 days of initial measles case exposure. Clinical outcome of IM ISG PEP recipients was determined by selective active surveillance and case self-reporting. IM ISG PEP failure was defined as onset of a measles-like rash 8–21 days post-IM ISG PEP. Post-IM ISG PEP measles IgG antibody level was tested in 8 recipients. Factors associated with measles disease were analyzed.ResultsSeventeen of 55 IM ISG PEP recipients developed clinically consistent measles in the following 8–21 days, corresponding to an estimated crude protective effectiveness of 69%. In school aged children 5–18 years, among whom potential exposure intensity and immune status confounders were considered less likely, estimated IM ISG PEP protective effectiveness was 50%. Age <25 years was significantly associated with breakthrough clinical measles in bivariate analysis (p = 0.0217). Among 8 tested contacts of 17 considered IM ISG PEP failures, post-IM ISG PEP measles IgG antibody levels (mean 16.3 days (range 16–17 days) post-PEP) were all <150 mIU/ml.ConclusionsThe estimated crude IM ISG PEP protective effectiveness against measles disease within 8–21 days post-ISG administration was 69%. Accuracy of this estimated protective effectiveness is vulnerable to assumptions and uncertainties in ascertaining exposure details and pre-exposure immune status. Increasing the Canadian recommended measles IM ISG PEP dose from 0.25 to 0.5 ml/kg (up to 15 ml maximum volume) may increase protective effectiveness.     

Proof-of-concept of a low-dose unmodified mRNA-based rabies vaccine formulated with lipid nanoparticles in human volunteers: A phase 1 trial

IntroductionIn a first-in-human study immune responses to rabies virus glycoprotein (RABV-G)-mRNA vaccine were dependent on the route of administration, necessitating specialized devices. Following successful preclinical studies with mRNA encapsulated in lipid nanoparticles (LNP), we tested an mRNA-LNP formulation (CV7202).MethodsIn this phase 1, multi-center, controlled study in Belgium and Germany we enrolled 55 healthy 18–40-year-olds to receive intramuscular injections of 5 μg (n = 10), 1 μg (n = 16), or 2 μg (n = 16) CV7202 on Day 1; subsets (n = 8) of 1 μg and 2 μg groups received second doses on Day 29. Controls (n = 10) received rabies vaccine, Rabipur, on Days 1, 8 and 29. Safety and reactogenicity were assessed up to 28 days post-vaccination using diary cards; immunogenicity was measured as RABV-G-specific neutralizing titers (VNT) by RFFIT and IgG by ELISA.ResultsAs initially tested doses of 5 μg CV7202 elicited unacceptably high reactogenicity we subsequently tested 1 and 2 μg doses which were better tolerated. No vaccine-related serious adverse events or withdrawals occurred. Low, dose-dependent VNT responses were detectable from Day 15 and by Day 29%, 31% and 22% of 1, 2 and 5 μg groups, respectively, had VNTs ≥ 0·5 IU/mL, considered an adequate response by the WHO. After two 1 or 2 μg doses all recipients had titers ≥ 0.5 IU/mL by Day 43. Day 57 GMTs were not significantly lower than those with Rabipur, which elicited adequate responses in all vaccinees after two doses. CV7202-elicited VNT were significantly correlated with RABV-G-specific IgG antibodies (r² = 0.8319, p < 0.0001).ConclusionsTwo 1 μg or 2 μg doses of CV7202 were well tolerated and elicited rabies neutralizing antibody responses that met WHO criteria in all recipients, but 5 μg had unacceptable reactogenicity for a prophylactic vaccine.ClinicalTrials.gov Identifier: NCT03713086.     

An accelerated rabies vaccine schedule based on toll-like receptor 3 (TLR3) agonist PIKA adjuvant augments rabies virus specific antibody and T cell response in healthy adult volunteers

BackgroundRabies is a fatal disease where post-exposure prophylaxis (PEP) is crucial in preventing infection. However, deaths even after appropriate PEP, have been reported. The PIKA Rabies vaccine adjuvant is a TLR3 agonist that activates B and T cells leading to a robust immune response.MethodsWe conducted a phase I, open label, randomized study in healthy adults to assess the safety and immunogenicity of the PIKA Rabies vaccine and an accelerated vaccine regimen. Thirty-seven subjects were randomized into 3 groups: control vaccine classic regimen, PIKA vaccine classic regimen and PIKA vaccine accelerated regimen. Subjects were followed up for safety, rabies virus neutralizing antibodies (RVNA) and T cell responses.ResultsBoth the control and PIKA Rabies vaccine were well tolerated. All adverse events (AEs) were mild and self-limiting. Seventy-five percent of subjects in the PIKA accelerated regimen achieved a RVNA titer ⩾0.5 IU/mL on day 7, compared to 53.9% in the PIKA classic regimen (p = 0.411) and 16.7% in control vaccine classic regimen (p = 0.012). The PIKA rabies vaccine elicited multi-specific rabies CD4 mediated T cell response already detectable ex vivo at day 7 after vaccination and that was maintained at day 42.ConclusionThe investigational PIKA rabies vaccine was well tolerated and more immunogenic than the commercially available vaccine in healthy adults.Clinical trial registry: The study was registered with clinicaltrials.gov NCT02657161.     

Epidemiologic Features of Animal Bite Cases Occurring in Rabies-Endemic Areas of Korea, 2005 to 2009

ObjectivesHuman rabies is a reemerging infectious disease in Korea. There was no human rabies case for 14 years until the disease had reoccurred in 1999. To prevent occurrence of human rabies, surveillance for animal bite patients in rabies endemic areas in Korea was conducted since 2005 as a part of a human rabies control program. The animal bite cases were analyzed to determine whether patients were treated according to the post-exposure prophylaxis (PEP) guideline of the Korea Centers for Disease Control and Prevention.MethodsInformation of animal bite cases that occurred from 2005 to 2009 in rabies high-risk regions were collected by cooperation with Regional Public Health Centers in 18 cities/districts of rabies endemic areas.ResultsA total of 2458 animal bite cases were reported. Dogs accounted for 86% of animal bites and 67% of the animals were not vaccinated against rabies virus. For PEP, among rabies-vaccinated animals, 92.7% were observed for clinical signs and 1.4% underwent necropsy. Among unvaccinated animals, 72.7% were observed for clinical signs and 4.1% underwent necropsy. The remaining animals were not available for examination. Of the animal bite patients, 32.5% received PEP and 51.6% were treated by first aid or by washing the wound.ConclusionsGiven that no human rabies cases were reported since 2005 and animal rabies was continuously reported in endemic areas of Korea, the human rabies control program implemented in 2005 appears to have a significant role in the prevention and control of human rabies.     

A randomized non-inferiority clinical study to assess post-exposure prophylaxis by a new purified vero cell rabies vaccine (Rabivax-S) administered by intramuscular and intradermal routes

BackgroundRabies is a 100% fatal disease but preventable with vaccines and immunoglobulins. We have developed a new purified vero cell rabies vaccine (Rabivax-S) and evaluated its safety and immunogenicity in post-exposure prophylaxis by intramuscular (IM) and intradermal (ID) routes.MethodsThis was a randomized active-controlled non-inferiority study in 180 individuals (age 5 years and above) with suspected rabies exposure (90 each with WHO Category II and Category III exposures). The participants received either Rabivax-S (1 mL IM; five doses), Rabivax-S (0.1 mL ID; eight doses) or purified chick embryo cell vaccine (PCEC, Rabipur®) (1 mL IM; five doses). The IM doses were given on Day 0, 3, 7, 14 and 28 while the ID doses were given on days 0, 3, 7 and 28. Category III patients also received a human rabies immunoglobulin (HRIG) on Day 0. Adverse events (AEs) were recorded with diary cards till day 42. Rabies neutralizing antibody levels were measured on day 0, 7, 14, 28 and 42.ResultsIn both the category II and III patients, the geometric mean concentration (GMC) ratios of Rabivax-S IM and Rabivax-S ID groups to PCEC IM were more than 1, thus proving the non-inferiority. GMCs were similar or higher in Rabivax-S groups at all the time points. Seroresponse against rabies (RFFIT titre ⩾ 0.5 IU/mL) was achieved in all participants. Mostly mild local and systemic adverse events were reported across the three groups and all resolved without sequelae.ConclusionsRabivax-S was well tolerated and showed immunogenicity comparable to a licensed rabies vaccine by both IM and ID routes in post-exposure prophylaxis.Registry No.: CTRI/2012/11/003135     

Inadequate antibody response to rabies vaccine in immunocompromised patient

We describe an inadequate antibody response to rabies vaccine in an immunocompromised patient. A literature search revealed 15 additional immunocompromised patients, of whom 7 did not exhibit the minimum acceptable level of antibodies after a complete postexposure prophylaxis regimen. An international rabies registry is needed to provide a basis for determining appropriate vaccination protocols.     

Seroconversion following incomplete human rabies postexposure prophylaxis

In August 2008, CDC and the Puerto Rico Department of Health conducted a serosurvey of patients who had discontinued rabies postexposure prophylaxis (PEP) prior to completing a schedule of five vaccine doses. The objective was to determine whether further vaccination of these patients was needed based on serum rabies neutralizing antibody levels. Eighteen patients consented to serology using the rapid fluorescent focus inhibition test. The World Health Organization's cutoff value of 0.5 IU/mL was used as the basis for recommending PEP continuance, while complete virus neutralization at the 1:5 dilution indicated seroconversion per current Advisory Committee for Immunization Practices recommendations. Serum samples were collected a median of 147 days (range 24–215) after receipt of the last vaccine dose. Ten patients were recommended for PEP continuance for titers below 0.5 IU/mL; however, of 11 patients, 33% of 2-dose, 100% of 3-dose, and 100% of 4-dose patients exhibited seroconversion. These findings corroborate previous studies that suggest a less than five-dose rabies vaccine regimen elicits adequate immunogenicity against rabies.     

Rabies post-exposure prophylaxis in malnourished children exposed to suspect rabid animals

Over half of the world's malnourished children live in Asia where more than 90% of reported human rabies deaths occur. In order to determine the effect of malnutrition on the immune response to rabies post-exposure prophylaxis (PEP), 45 children with moderate to severe protein energy malnutrition (PEM) who were exposed to potentially rabid animals were enrolled in a clinical trial. Patients received purified chick embryo cell rabies vaccine (PCECV) on days 0, 3, 7, 14 and 30. Blood was drawn on days 0, 14 and 30 and evaluated for the presence of rabies virus neutralizing antibody. All children that met the protocol criteria developed rabies virus neutralizing antibody titers above the acceptable level of 0.5 IU/mL by day 14 and no serious adverse events were reported. We conclude that children in this study that received four or five doses of rabies vaccine intramuscularly developed an acceptable immune response despite their severe degree of protein energy malnutrition.     

Previous SARS-CoV-2 Infection,Age, and Frailty Are Associated With 6-Month Vaccine-Induced Anti-Spike Antibody Titer in Nursing Home Residents

ObjectivesOlder nursing home residents make up the population at greatest risk of morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No studies have examined the determinants of long-term antibody responses post vaccination in this group.DesignLongitudinal cohort study.Setting and ParticipantsResidents from 5 nursing homes assessed before vaccination, and 5 weeks and 6 months post vaccination, with the BNT162b2 messenger RNA SARS-CoV-2 vaccine.MethodsComprehensive clinical assessment was performed, including assessment for comorbidity, frailty, and SARS-CoV-2 infection history. Serum nucleocapsid and anti-spike receptor binding domain (RBD) antibodies were analyzed at all timepoints. An in vitro angiotensin-converting enzyme (ACE2) receptor-spike RBD neutralization assay assessed serum neutralization capacity.ResultsOf 86 participants (81.1 ± 10.8 years; 65% female), just under half (45.4%; 39 of 86) had evidence of previous SARS-CoV-2 infection. All participants demonstrated a significant antibody response to vaccination at 5 weeks and a significant decline in this response by 6 months. SARS-CoV-2 infection history was the strongest predictor of antibody titer (log-transformed) at both 5 weeks [β: 3.00; 95% confidence interval (CI): 2.32–3.70; P < .001] and 6 months (β: 3.59; 95% CI: 2.89–4.28; P < .001). Independent of SARS-CoV-2 infection history, both age in years (β: ?0.05; 95% CI: ?0.08 to ?0.02; P < .001) and frailty (β: ?0.22; 95% CI: ?0.33 to ?0.11; P < .001) were associated with a significantly lower antibody titer at 6 months. Anti-spike antibody titers at both 5 weeks and 6 months significantly correlated with in vitro neutralization capacity.Conclusions and ImplicationsIn older nursing home residents, SARS-CoV-2 infection history was the strongest predictor of anti-spike antibody titers at 6 months, whereas age and frailty were independently associated with lower titers at 6 months. Antibody titers significantly correlated with in vitro neutralization capacity. Although older SARS-CoV-2 naïve nursing home residents may be particularly vulnerable to breakthrough SARS-CoV-2 infection, the relationship between antibody titers, SARS-CoV-2 infection, and clinical outcomes remains to be fully elucidated in this vulnerable population.     

Immunogenicity of the hepatitis B vaccine adjuvanted with AS04C in patients with biological therapies

BackgroundHepatitis B vaccination is necessary for patients with biologic therapies because of the immunomodulatory effect of these drugs. Due to the elevated use of these therapies in the latest years, the research for new vaccination regimens and the improvement of the current ones is essential. New adjuvants like AS04C might be a potential strategy to improve immune response. Hepatitis B vaccine adjuvanted with AS04C has not been studied in this population before.We analyzed the immunogenicity of an adjuvanted hepatitis B vaccine in patients with biologic therapies. Variables that might affect vaccine response were also evaluated.MethodsAnalytic observational retrospective cohort study performed between January 2016 and September 2018. 301 patients under biological treatment aged from 18 years were included. Patients received 4 doses of hepatitis B adjuvanted vaccine (Fendrix®) in a 0–1–2–6 month immunization schedule. Several sociodemographic, clinical and pharmacological variables were evaluated. The outcome variable was measured as the antibody titers (anti-HBs). The geometric mean of titers (GMT) as a measure for the central tendency was calculated from these values.ResultsThe immunization schedule of the hepatitis B vaccine adjuvanted with AS04C demonstrated high levels of seroconversion with 82.1 % (95 % CI, 77.6–86.6) of vaccinated patients seroconverting after primary vaccination and achieving 89.0 % (95 % IC, 85.3–92.7) after the booster doses for non-responders. The use of corticosteroid therapy and high doses of them, age over 60 years and the main diagnosis were associated with lower seroconversion rates and lower anti-HBs titers.ConclusionsThe hepatitis B vaccine adjuvanted with AS04C (Fendrix®) produces an adequate immune response in patients with autoimmune diseases and immunosuppressive and/or immunomodulating therapies. This immunization schedule is proposed as a very suitable and adapted option for the protection of patients with autoimmune diseases under active biological therapies.     

Humoral anti-SARS-CoV-2 immune response after two doses of Comirnaty vaccine in nursing home residents by previous infection status

BackgroundCoronavirus disease 2019 (COVID-19) is associated with increased morbidity and mortality in older adults. Although the advent of the first vaccines has significantly reduced these rates, data on older adults in clinical trials are scarce.ObjectivesWe quantified and compared the humoral response in individuals with vs. without pre-existing seropositivity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in a cohort of 69 patients living in a nursing home and who had received the recommended two doses of the Comirnaty (Pfizer-BioNTech®) vaccine.ResultsAll 69 patients (100%) tested positive for antibodies against SARS-CoV-2 at 2 months post-vaccination. Residents with a pre-vaccination infection had significantly higher titers of anti-spike 1 IgG than those with no prior infection (median [interquartile range]: 55,726 [14463–78852] vs. 1314 [272–1249] arbitrary units, respectively; p < 0.001). The same result was observed for neutralizing antibodies titers (704 [320–1280] vs. 47 [20–40] respectively; p < 0.001). Between the pre-vaccination and post-vaccination periods, for IgG and neutralizing antibodies, we observed a 49 and 8-fold increase respectively. In comparison to the wild-type Receptor Binding Domain (RBD), the binding capacity of these vaccine sera was significantly decreased on the B.1.351 and P.1 variants RBD but not decreased with respect to the B.1.1.7 RBD.Although all nursing home residents developed a humoral response following Comirnaty vaccine, its intensity appeared to depend on the pre-vaccination serological status.ConclusionOur results raise the question of how many doses of vaccine should be administered in older and how long the protection will be effective.     

Seroprevalence of Bordetella pertussis antibodies and anti-pertussis antibody response after a single dose of reduced-antigen combined diphtheria,tetanus, and acellular pertussis vaccine (Tdap) in pregnant Thai women

BackgroundMaternal immunization with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) has recently been implemented to prevent infant pertussis. Tdap is still not routinely recommended in Thailand, and there are limited data to support or challenge this strategy.ObjectivesThe primary aim was to determine the seroprevalence of anti-pertussis toxin antibodies (anti-PT IgG) among pregnant Thai women. The secondary aims were to evaluate antibodies response after Tdap vaccination between seronegative and seropositive mothers and to compare the different antibody titers at delivery among seropositive mothers who received Tdap to those who received tetanus-diphtheria vaccine (Td).MethodsThis randomized clinical trial was conducted during April 2018 to April 2019 at Siriraj Hospital, Bangkok, Thailand. A total of 129 pregnant women were included. Paired blood samples for anti-PT IgG levels were obtained during the first antenatal visit and at delivery. A baseline cut-off value of <5 IU/ml indicated seronegativity. There were 29 exclusions from the original 129 enrollment. All seronegative participants (n = 69) received Tdap, while the seropositive group were randomized 1:1 to receive either Tdap (n = 18) or Td (n = 13) during 27–36 weeks’ gestation. The antibody levels from both sera were compared between groups.ResultsThe seroprevalence of maternal anti-PT IgG was 33.3% (43/129). There was no significant difference in the increment of antibody levels after Tdap vaccination between the seronegative and seropositive groups (30.2 vs. 42 IU/ml; p = 0.183). Among seropositive groups, all Tdap recipients had increased antibody titers at delivery, while all Td recipients showed waning of immunity throughout gestation. (42 IU/ml vs. −7.4 IU/ml; p < 0.001).ConclusionMost pregnant Thai women have seronegative against pertussis. Most seropositive mothers had initial low antibody titers and their immunity significantly decreased before delivery. Our findings highlight the need for universal pertussis immunization in pregnancy regardless of individual baseline immunity.     

Seroprevalence of antibodies against the three serotypes of poliovirus and IPV vaccine response in adult solid organ transplant candidates

ObjectivesTo assess the prevalence of protective antibody titers to polioviruses in adults candidates for solid organ transplant (SOT), and to assess the immunogenic response to inactivated polio vaccine in this population.MethodsThe study included SOT candidates referred to Immunization Reference Centre of Evandro Chagas National Institute of Infectious Diseases from March 2013 to January 2016. It was conducted in 2 phases. The first one, a cross-sectional seroprevalence study, followed by an uncontrolled analysis of vaccine response among patients without protective antibody titers at baseline. Antibody titers to poliomyelitis were determined by microneutralization assay.ResultsAmong 206 SOT candidates included, 156 (76%) had protective antibody titers to all poliovirus serotypes (95% CI: 70–81%). Proven history of oral vaccination in childhood was not associated with higher seroprevalence of protective antibody. In 97% of individuals without protective antibody titers at baseline, there was adequate vaccine response with one dose of inactivated polio vaccine.ConclusionsA relevant proportion of adult candidates for SOT does not have protective titers of antibodies to one or more poliovirus serotype. One dose of inactivated vaccine elicited protective antibody titers in 97% of these subjects and should be routinely prescribed prior to SOT.