Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in rhesus macaques coincides with anamnestic antibody response in the lung.

mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. Here, we immunized rhesus macaques and assessed immune responses over 1 year in blood and upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID50 at weeks 6 (peak) and 48 (challenge), respectively. Antibody-binding titers also decreased in bronchoalveolar lavage (BAL). Four days after Delta challenge, the virus was unculturable in BAL, and subgenomic RNA declined by ∼3-log10 compared with control animals. In nasal swabs, sgRNA was reduced by 1-log10, and the virus remained culturable. Anamnestic antibodies (590-fold increased titer) but not T cell responses were detected in BAL by day 4 post-challenge. mRNA-1273-mediated protection in the lungs is durable but delayed and potentially dependent on anamnestic antibody responses. Rapid and sustained protection in upper and lower airways may eventually require a boost.

[Breast cancer : individualized risk assessment for tailor-made screening]. / Cancer du sein : évaluation individualisée du risque en vue d'un dépistage sur mesure.

Breast cancer is the leading cause of neoplastic death in women around the world. In the era of personalized medicine, legitimately awaited by our patients, the future of breast cancer screening will depend on an individual-based risk assessment, making it possible to better adapt the age of onset, frequency and the type of examinations useful for this screening. This article reviews the three broad categories of highest risk factors available to establish a risk score appropriate for each patient.

Le cancer du sein est la première cause de mortalité par néoplasie chez la femme de par le monde. À l'ère d'une médecine personnalisée, légitimement attendue par nos patientes, l'avenir du dépistage du cancer du sein passera par une évaluation du risque sur base individuelle, permettant d'adapter, au mieux, l'âge de début ainsi que la fréquence et le type des examens utiles pour ce dépistage. Cet article passe en revue les trois grandes catégories de facteurs de plus haut risque disponibles pour établir un score de risque adapté à chaque patiente.

Psychometric evaluation of the Chinese version of the Fonseca anamnestic index for temporomandibular disorders.

BACKGROUND: The Fonseca anamnestic index (FAI) offers a simple, low-cost, patient-reported method for screening temporomandibular disorders (TMDs). OBJECTIVES: This study described the development of the Chinese version of the FAI (FAI-C) and examined its reliability and validity when compared to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). METHODS: The FAI-C was created by translation and cross-cultural adaptation of the English instrument following international guidelines. Psychometric evaluation of the FAI-C was carried out on a sample of 613 patients with TMDs and 57 controls. Reliability of the FAI-C was determined by means of internal consistency and test-retest methods while validity was ascertained by criterion-related validity. Criterion validity was examined via Cohen's kappa, sensitivity and specificity when compared with DC/TMD Axis I diagnoses. RESULTS: Cronbach's alpha value (internal consistency) for total FAI-C score was 0.669, and intra-class correlation coefficient (ICC) value (test-retest reliability) was 0.823. For criterion validity, kappa coefficient value was 0.633 while sensitivity and specificity was 95.9% and 71.9%, respectively. CONCLUSION: The Chinese version of the FAI demonstrated acceptable reliability and good validity. The FAI-C could thus be used as an instrument for screening TMDs in Chinese literate populations.

Persistence of HBsAg-specific antibodies and immune memory two to three decades after hepatitis B vaccination in adults.

The duration of protection after hepatitis B vaccination is not exactly known. This phase IV study evaluated antibody persistence and immune memory 20-30 years after adult immunization with recombinant hepatitis B vaccine (HBsAg vaccine, Engerix-B) in routine clinical practice. Men and women 40-60 years old, with documented evidence of vaccination with three or four HBsAg vaccine doses 20-30 years earlier and without subsequent booster, were enrolled and received HBsAg vaccine as challenge dose. HBsAg-specific antibodies (anti-HBs) and frequencies of HBsAg-specific circulating memory B cells and CD4+ T cells expressing combinations of activation markers (CD40L, IL2, IFNγ, TNFα) were measured prechallenge, 7 and 30 days postchallenge. Of 101 participants in the according-to-protocol cohort for immunogenicity, 90.1% had anti-HBs concentrations ≥ 10 mIU/mL prechallenge administration; 84.2% and 100% mounted an anamnestic response 7 and 30 days postchallenge, respectively. HBsAg-specific memory B and CD4+ T cells expressing at least two activation markers were low prechallenge and increased markedly postchallenge. These results suggest sustained immune memory and long-term protection 20-30 years after a complete primary HBsAg vaccination course during adulthood, in line with current recommendations that a booster is not needed in fully vaccinated immunocompetent adults.

Immunogenicity and safety of 4 vs. 3 standard doses of HBV vaccination in HIV-infected adults with isolated anti-HBc antibody.

BACKGROUND: Presence of isolated anti-HBc antibody is common in HIV-infected patients in endemic areas and could be caused by prior HBV infection with loss of anti-HBs antibody. The role of vaccination in these patients remains controversial and is based largely on limited and low quality data. We, therefore, conducted this study to determine immunogenicity and safety of 4 vs. 3 standard doses of HBV vaccination in HIV-infected adults with isolated anti-HBc antibody. METHODS: An open-label, randomized controlled trial was conducted among HIV-infected patients visiting HIV clinic of the Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand between July and September 2017. Inclusion criteria included ≥ 18 years of age, currently on a stable antiretroviral regimen, CD4+ cell count ≥ 200 cells/mm3, plasma HIV-1 RNA < 20 copies/mL, and isolated anti-HBc antibody. The participants were randomized to receive either 3 standard doses (20 µg at month 0, 1, 6) or 4 standard-doses (20 µg at month 0, 1, 2, 6) of IM HBV vaccination, and were evaluated for anamnestic response at week 4 and vaccine response at week 28. RESULTS: Of the 97 patients screened, 54 (32 male, mean age of 46 years) were enrolled and 27 were allocated to each of the vaccination groups. Anamnestic response occurred in 25.9% vs. 33.3% in 3-dose group vs. 4-dose group, respectively (p = 0.551). The vaccine response rates at week 28 were 85.2% in 3-dose group vs. 88.9% in 4-dose group (p = 1.000); geometric mean titer of anti-HBs antibody at week 28 was 63.8 and 209.8 mIU/mL in 3-dose group and 4-dose group, respectively (p = 0.030). No adverse events were reported. CONCLUSIONS: An anamnestic response occurred in one-third of Thai HIV-infected patients with isolated anti-HBc antibody who received one dose of HBV vaccination; however, the majority were still unprotected. The use of either 3 or 4 standard-doses of vaccination was highly effective and should be recommended in all HIV-infected individuals with isolated anti-HBc antibody. Trial registration ClinicalTrials.gov; NCT03212911. Registered 11 July 2019, https://clinicaltrials.gov/ct2/show/NCT03212911.

Prevalence and Severity of Temporomandibular Disorders among Undergraduate Medical Students in Association with Khat Chewing.

INTRODUCTION: The aim of this study was to assess the prevalence and severity of temporomandibular joint disorders (TMDs) among undergraduate medical students in the presence of khat chewing over a period of time. MATERIALS AND METHODS: Totally, 186 medical college students (age < 20 years) were randomly selected for the present study. The study subjects were divided into two groups according to age, under 20 and above 20 years. The study was based on Fonseca's anamnestic index and its questionnaire, which is composed of 10 questions and classifies the severity of TMDs. The obtained data were coded and entered into Statistical Package for the Social Sciences (SPSS) program for analysis using chi-square test at significance level of 5%. RESULTS: Most of the participants were male (68.8%) students and older than 20 years (63%). Those who reported with khat chewing comprised 31.7%. From the total samples, only 38.0% was classified as having mild TMD and 0.50% were classified as having severe TMD. Poor dental articulation, grinding of teeth, headaches, tense personalities, and temporomandibular joint (TMJ) clicking were the most common clinical findings. The mean scores showed no significant difference among gender (p < 0.29) and the khat chewing (p < 0.531) groups for the 10 questions. However, it showed significant difference among age groups (p < 0.025). CONCLUSION: The majority of subjects complained of mild TMD, while only a few cases showed a moderate TMD among different age groups. The most frequently reported dysfunctions were related to poor dental articulation and grinding of the teeth, frequent headaches, the clicking of joint, and tense personalities. No significant difference was found between gender and khat and nonkhat chewing groups. CLINICAL SIGNIFICANCE: Khat chewing is a parafunctional habit and affects dental occlusion (especially cuspal wear) in terms of anterior guidance. Such alterations in occlusion are known to be one of the causative (predisposing) factors of TMD.

Anamnestic responses in pigs to the Taenia solium TSOL18 vaccine and implications for control strategies.

Specific antibody responses were assessed in pigs immunized with the Taenia solium vaccine TSOL18. Anti-TSOL18 responses were compared 2 weeks after secondary immunization, where the interval between primary and secondary immunization was 4, 8, 12, 16 or 20 weeks. All animals responded to the vaccine and there was no diminution in antibody responses in animals receiving their second injection after an interval up to 20 weeks. Pigs receiving vaccinations at an interval of 12 weeks developed significantly increased antibody responses compared with animals receiving immunizations 4 weeks apart (P = 0.046). The ability to deliver TSOL18 vaccination effectively where the revaccination schedule can be delayed for up to 12-16 weeks in pigs increases the options available for designing T. solium control interventions that incorporate TSOL18 vaccination.

Immune Response And Anamnestic Immune Response In Children After A 3-Dose Primary Hepatitis B Vaccination.

BACKGROUND: Diseases caused by Hepatitis B virus (HBV) have a worldwide distribution. Pakistan adopted the recommendations of World Health Organization (WHO) for routine universal infant vaccination against hepatitis B in 2002, currently being administered at 6, 10, and 14 weeks of age in a combination vaccine. This study was conducted to determine the immune response & anamnestic immune response in children, 9 months-10 years of age, after a 3dose primary Hepatitis B vaccination. METHODS: This cross sectional study was conducted in the Department of Paediatrics, King Edward Medical University/Mayo Hospital, Lahore, Pakistan, from January to June, 2014. A total of 200 children of either sex between the ages of 9 months to 10 years, documented to have received 3 doses of hepatitis B vaccines according to Expanded Program of Immunization (6,10,14 weeks) schedule in infancy, were recruited by consecutive sampling. The level of serum antiHBsAb by ELIZA was measured. Children with antiHBs titers ≥10 mIU/mL were considered to be immune. Those with anti HBsAb levels <10 mIU/mL were offered a booster dose of infant recombinant hepatitis B vaccine. The second serum sample was obtained 21-28 days following the administration of the booster dose and the anamnestic immune response was measured. Data was analysed using SPSS 17 to determine the relation between time interval since last vaccination and antibody titer. Chi square test was applied. RESULTS: Of the 200 children, protective antibody response was found in 58%. Median serological response was 18.60 (range 2.82 - 65.15). Antibody levels were found to have a statistically significant ( pvalue 0.019) negative correlation with the time since last administration of vaccine. A booster dose of Hepatitis B vacci ne was administered to all nonresponders, with each registering a statistically significant (pvalue 0.00) anamnestic response. CONCLUSIONS: The vaccination schedule with short dosage interval was unable to provide protection to 42% of the study population. Introduction of birth dose of Hepatitis B vaccine to the existing schedule is recommended.

Immune memory response induced in vitro by recombinant hepatitis B surface antigen challenge 13-18 years after primary vaccination.

The question of whether booster doses are required to maintain long-term protection against hepatitis B virus (HBV) after primary vaccination remains to be determined. Thus, the aim of this study was to evaluate the immune memory responses to hepatitis B surface antigen (HBsAg) challenge in vaccinated individuals through an in vitro-specific stimulation assay. Peripheral blood mononuclear cells (4 × 10(6) cells/ml) were stimulated with 50 ng/ml of recombinant HBsAg. In vitro anamnestic antibody responses, as shown by detection of high avidity antibody in culture supernatants, were found 13-18 years after primary vaccination and were not correlated with serum antibodies (r = -0.177; P = 0.377). In addition, the findings from this study indicate that immune memory against hepatitis B was well preserved in 40.0% and 60.0% of vaccinees with anti-HBs levels less than 10 IU/L or lacking serum antibodies altogether, respectively. In conclusion, the data suggest the presence of immunological memory in vaccinated individuals, including those who showed anti-HBs <10 IU/L or undetectable antibody.

Antibody levels following vaccination of beef calves with a tetanus toxoid.

Tetanus is a preventable, yet often fatal, disease affecting many species, including beef cattle. Vaccination for tetanus is recommended for calves at high risk of disease, but typical beef cattle management practices often make adherence to vaccine manufacturers' guidance for a second (booster) dose of vaccine difficult. This study examined the antibody response following a single dose of tetanus toxoid, as well as following booster vaccination at various intervals. Anti-tetanus IgG antibodies were detectable 25 days (D25) after a single dose, and rose following booster at either D25 D109 after initial vaccination. Antibody levels then declined numerically from D109 to D179 for calves boostered at D25 but rose on D179 for those receiving a second dose on D109. The relatively rapid response in IgG production, even in the absence of a booster vaccine, may suggest value in vaccinating calves for tetanus at time of greatest risk, even if a booster cannot be administered. The study also provides support for priming of the immune response lasting at least until D109 after primary immunization.

Psychometric properties of the Fonseca Anamnestic Index (FAI) for temporomandibular disorders: Turkish version, responsiveness, reliability, and validity study.

PURPOSE: Many assessment tools have been proposed for use in clinical practice and research on individuals with temporomandibular disorders (TMD). It aimed to translate the Fonseca Anamnestic Index into Turkish (FAI/T) and examine the responsiveness, reliability and validity of the FAI/T in this study. MATERIALS AND METHODS: Two hundred forty-nine individuals (207 female/42 male) with TMD were included in this study according to the RDC/TMD (muscle disorders, disc displacement, arthralgia and mixed disorders (muscle disorders and disc displacement)). Reliability was evaluated with test-retest reliability, internal consistency, and reproducibility. Validity was assessed with structural validity, construct validity, content validity, and face validity. In addition, responsiveness and floor and ceiling effects were also examined. RESULTS: The ICC value (0.906) and Cronbach's α (0.951) of the (FAI/T) were excellent. Following Explarotary Factor Analysis, two factors were extracted, accounting for 51.859% of the total variation. Structural validity, construct validity, content validity, and face validity analyses proved the validity of the FAI/T. The responsiveness analysis showed that the Turkish FAI and its subscales were able to detect change over time. CONCLUSIONS: The FAI/T has shown excellent reliability and good validity. The FAI/T can assess the symptoms of Turkish-speaking persons with TMD.Clinical Trials registration number: NCT04274985.

Turkish version of Fonseca Anamnestic Index has been translated into Turkish from English version.Turkish version of Fonseca Anamnestic Index has excellent reliability and good validity.The Turkish version of the Fonseca Anamnestic Index and its subscales are able to detect change over time.Turkish clinicians and researchers could easily use the Turkish version of the Fonseca Anamnestic Index to assess the Turkish population with temporomandibular disorders.

Development and evaluation of a software system for medical students to teach and practice anamnestic interviews with virtual patient avatars.

BACKGROUND AND OBJECTIVES: Taking a medical history is a core competence of the diagnostic process. At the beginning of their study medical students need to learn and practice the necessary techniques, initially focusing on good structuring and completeness. For this purpose, an interactive software system (ViPATalk) was developed in which the student can train to pose questions to virtual patient avatars in free conversation. At the end, the student receives feedback on the completeness of the questioning and an explanation of the essential items. The use of this software was compared to the traditional format of student role play in a randomized trial. METHODS: The central component of ViPATalk is a chatbot based on the AI language AIML, which generates an appropriate answer based on keywords in the student's question. To enable a realistic use, the student can enter the question via microphone (speech-to-text) and the answer generated by the chatbot is presented as a short video sequence, where the avatar is generated from a real image. Here, the transition between the sequences is seamless, resulting in a continuous movement of the avatar during the conversation. RESULTS: The learning success by practicing with ViPATalk was tested in an anamnestic interview with actors as simulated patients. The completeness of the conversation was evaluated with regard to numerous aspects and also certain behaviors during the conversation. These results were compared with those after practicing using peer role play. CONCLUSIONS: It was found that practicing with ViPATalk was mostly equivalent to the students' role play. In the subsequent survey of the students, the wish was expressed that the ViPATalk software should also be used as an online tool for self-study and that there should be more cases for practicing.

Assessment of the severity of temporomandibular disorders in females: Validity and reliability of the Fonseca anamnestic index.

OBJECTIVE: To evaluate the validity and reliability of the Fonseca anamnestic index (FAI) over time in Turkish females. METHODS: Four hundred-fourteen patients who visited the otorhinolaryngology clinic were initially included in the study between January 1, 2018 and January 1, 2019. The Turkish version of the FAI is a self-report instrument that was completed by all of the patients after a brief explanation from the clinician. Cronbach's alpha was calculated using data from the first questionnaire. RESULTS: The results of the first assessment showed 243 patients had no TMD (58.7%), 40 had mild TMD (9.7%), 87 had moderate TMD (21%), and 44 had severe TMD (10.6%). At the second assessment, the respective values were 243 (58.7%), 37 (8.9%), 98 (23.7%), and 36 (8.7%). The internal consistency of the first test was high. CONCLUSION: The FAI can be used to collect a large amount of data easily, at minimal cost.

The accuracy and reliability of the Turkish version of the Fonseca anamnestic index in temporomandibular disorders.

OBJECTIVE: To determine the reliability and diagnostic accuracy of the Turkish version of the Fonseca anamnestic index (FAI-T). METHODS: The cultural equivalence of the FAI was established according to the International Network for Orofacial Pain and Related Disorders Methodology. The test-retest reliability, internal consistency, and diagnostic accuracy of the FAI-T was carried out in a sample of 66 controls and 139 patients with TMD. Diagnostic accuracy of the FAI-T was evaluated against the Research Diagnostic Criteria for Temporomandibular Disorders. RESULTS: Internal consistency analysis resulted in a Cronbach's alpha coefficient of 0.805. The intraclass correlation coefficient (ICC) values of each index question ranged from 0.739 to 0.897. FAI had a high level of accuracy (area under the ROC curve of 0.928). CONCLUSION: The results provide considerable evidence that the FAI-T can be used as a screening tool for the identification of TMD in Turkish-speaking populations.

Does childhood maltreatment play a role in temporomandibular disorders?

The aim of this study was to find out if experiences of maltreatment in childhood have an effect on the occurrence of temporomandibular joint disorders (TMD). The study was conducted on 380 volunteer adults (252 females and 128 males), with a mean (SD) age of 27.63 (9.06) years. The level of TMD was assessed using the Fonseca Anamnestic Index (FAI). Childhood Trauma Questionnaires (CTQ) were completed by the participants and their marital status and educational level were recorded. FAI scores were significantly higher in females than in males. There was no statistically significant difference between gender and total CTQ score. Moreover, there was no statistically significant difference between educational status, marital status, and total CTQ score. FAI scores correlated positively with total CTQ scores in all individuals. Similarly FAI scores correlated positively with total CTQ scores in males and females. Childhood maltreatment is associated with TMDs. Dentists should be aware that possible collaboration with psychiatrists and/or psychologists when treating patients with TMD could increase the success of their treatment.

TMD diagnosis: Sensitivity and specificity of the Fonseca Anamnestic Index.

OBJECTIVE: To verify whether the Fonseca Anamnestic Index (FAI) has adequate sensitivity and specificity to be used in the diagnosis of temporomandibular disorder (TMD). METHODS: Two hundred-sixty-five participants with symptoms of TMDs were assessed through the FAI and through the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and then classified as sick or non-sick. The sensitivity, specificity, and predictive values of the FAI in relation to the RDC/TMD were calculated using the STATA 14.0 software. RESULTS: Most of the patients were female, white, without a steady job, and the average age was 37.57 years. The FAI showed high sensitivity (97.21%) but obtained a low specificity (26.00%). The positive and negative predictive values were 84.96% and 68.42%, respectively. CONCLUSION: The FAI is very sensitive in identifying patients who actually have TMD but not very specific in identifying non-TMD patients, being indicated only for initial screening of patients.

Temporomandibular Disorder Prevalence and Its Association with Lifestyle Habits in Biomedicine Students-A Cross-Sectional Study.

This study aimed to examine the frequency of temporomandibular disorder among biomedical students and relate its occurrence to lifestyle habits. A cross-sectional collection of data was carried out and included a total of 676 examinees through a questionnaire that had 73 questions: general information and lifestyle habits, the Fonseca Anamnestic index (FAI), the Jaw Function Limitation Scale (JFLS), and the Perceived Stress Questionnaire (PSQ). The statistical analyses between three or more groups were conducted using the one-way analysis of variance (ANOVA) with post hoc Scheffé test or Kruskal-Wallis test with post hoc Dunn's test for quantitative variables. The comparison of qualitative variables was conducted using the Chi-square test, while the correlations were determined using Spearman's correlation test. The analysis showed that a higher frequency of moderate or severe TMD was observed in subjects who were smokers (p < 0.001) compared to non-smokers. Subjects who consumed more coffee had moderate to severe TMD compared to subjects who consumed a lesser amount (p < 0.001). Furthermore, a positive correlation between the amount of stress and the severity of TMD was found. Our study implies that students of biomedical studies have an increased risk for TMD and that there is a link with their lifestyle habits.

Demonstration of durable hepatitis B immune memory in children vaccinated with a DTaP5-IPV-HepB-Hib infant-toddler series 7 to 8 years previously.

Vaccination against hepatitis B (HepB) provides long-term protection against infection. This is despite a reduction in HepB surface antibody (anti-HBs) concentrations over time to levels below the well-accepted correlate of protection of ≥10 mIU/mL. Continued evidence of immune memory and protection despite declined anti-HBs concentrations can be demonstrated by HepB virus surface antigen challenge studies. Long-term immune memory and protection against HepB infection has not been demonstrated previously for the pediatric hexavalent vaccine DTaP5-IPV-HepB-Hib. This phase 3, multicenter, single-group, open-label challenge study (NCT04490499; EudraCT: 2020-000126-26) evaluated immune memory against HepB infection in children who had received DTaP5-IPV-HepB-Hib at 2, 4, and 11-12 months of age, or at 2, 3, 4, and 12 months of age. At age 8-9 years, they were each challenged with 5 µg of monovalent HepB vaccine. Anti-HBs levels were measured on pre-challenge day 1 and post-challenge day 30. At baseline, 45.4% (93 of 205) had anti-HBs levels ≥10 mIU/mL. On post-challenge day 30, 99.5% (201 of 202) had anti-HBs levels ≥10 mIU/mL, regardless of initial vaccination schedule. Post-challenge, geometric mean concentrations increased 71-fold over baseline and 96.0% of children had a ≥4-fold rise in anti-HBs concentrations with similar results across both dosing schedules. The challenge dose was well tolerated. The robust anti-HBs responses after a single 5-µg dose of HepB vaccine confirm the persistence of a HepB immune memory and demonstrate that DTaP5-IPV-HepB-Hib provides long-term protection against HepB.

B Cell Responses upon Human Papillomavirus (HPV) Infection and Vaccination.

Infection with human papillomavirus (HPV) is the necessary cause of cervical cancer. Availability of vaccines against HPV makes it a highly preventable disease. HPV vaccines act through type-specific neutralizing antibodies produced by antigen-specific plasma cells known as long-lived plasma cells (LLPC). However, just as any other vaccine, success of HPV vaccine is attributed to the immunologic memory that it builds, which is largely attained through generation and maintenance of a class of B cells named memory B cells (Bmem). Both LLPCs and Bmems are important in inducing and maintaining immune memory and it is therefore necessary to understand their role after HPV vaccination to better predict outcomes. This review summarizes current knowledge of B-cell responses following HPV vaccination and natural infection, including molecular signatures associated with these responses.

Antibody persistence and immune memory response following primary vaccination and boosting with live attenuated SA 14-14-2 Japanese encephalitis vaccine (CD-JEV) in Bangladesh: A phase 4 open-label clinical trial.

INTRODUCTION: Japanese encephalitis (JE) virus is one of the leading causes of viral encephalitis across temperate and tropical zones of Asia. The live attenuated SA 14-14-2 JE vaccine (CD-JEV) is one of three vaccines prequalified by the World Health Organization (WHO) to prevent JE. WHO currently recommends a single CD-JEV dose for infants in endemic settings. However, in the absence of long-term immunogenicity data, WHO has indicated a need for long-term immunogenicity studies to inform optimal dosing schedules and determine the need for booster doses. METHODS: This Phase 4, open-label clinical study measured neutralizing antibody (NAb) titers in Bangladeshi children three and four years after primary CD-JEV vaccination and 7 and 28 days after a booster CD-JEV vaccination given four years after primary vaccination. The study also assessed the tolerability and safety of the booster dose. A NAb titer of ≥1:10 was considered seroprotective. RESULTS: Of 560 children vaccinated between 10 and 12 months of age with CD-JEV three years earlier and enrolled in this study from 30 July 2015 through 03 January 2016, 52 (9.3%; 95% CI: 7.2-12.0) had a seroprotective titer at enrollment. One year later, of 533 children, 66 (12.4%; 95% CI: 9.9-15.5) had a seroprotective titer before receiving a booster dose. Of 524 children who received a booster CD-JEV dose, 479 (91.4%; 95% CI: 88.7-93.5) and 514 (98.1%; 95% CI: 96.5-99.0) were seroprotected 7 and 28 days later, respectively. The geometric mean titer (GMT) was 6 (95% CI: 6-6) at baseline, 105 (95% CI: 93-119) 7 days post-booster, and 167 (95% CI: 152-183) 28 days post-booster. No vaccine-associated neurologic adverse events or other serious adverse events were noted following the booster dose. CONCLUSIONS: Although most children did not have measurable antibody titers three and four years after a single primary CD-JEV dose, more than 90% of seronegative children had a strong anamnestic response within one week of a booster dose. This suggests that these children were immune despite the absence of measurable NAb prior to their booster.ClinicalTrials.gov Identifier: NCT02514746.