Safety and Reactogenicity of Canarypox ALVAC-HIV (vCP1521) and HIV-1 gp120 AIDSVAX B/E Vaccination in an Efficacy Trial in Thailand

A prime-boost vaccination regimen with ALVAC-HIV (vCP1521) administered intramuscularly at 0, 4, 12, and 24 weeks and gp120 AIDSVAX B/E at 12 and 24 weeks demonstrated modest efficacy of 31.2% for prevention of HIV acquisition in HIV-uninfected adults participating in a community-based efficacy trial in Thailand.Reactogenicity was recorded for 3 days following vaccination. Adverse events were monitored every 6 months for 3.5 years, during which pregnancy outcomes were recorded. Of the 16,402 volunteers, 69% of the participants reported an adverse event any time after the first dose. Only 32.9% experienced an AE within 30 days following any vaccination. Overall adverse event rates and attribution of relatedness did not differ between groups. The frequency of serious adverse events was similar in vaccine (14.3%) and placebo (14.9%) recipients (p = 0.33). None of the 160 deaths (85 in vaccine and 75 in placebo recipients, p = 0.43) was assessed as related to vaccine. The most common cause of death was trauma or traffic accident. Approximately 30% of female participants reported a pregnancy during the study. Abnormal pregnancy outcomes were experienced in 17.1% of vaccine and 14.6% (p = 0.13) of placebo recipients. When the conception occurred within 3 months (estimated) of a vaccination, the majority of these abnormal outcomes were spontaneous or elective abortions among 22.2% and 15.3% of vaccine and placebo pregnant recipients, respectively (p = 0.08). Local reactions occurred in 88.0% of vaccine and 61.0% of placebo recipients (p<0.001) and were more frequent after ALVAC-HIV than AIDSVAX B/E vaccination. Systemic reactions were more frequent in vaccine than placebo recipients (77.2% vs. 59.8%, p<0.001). Local and systemic reactions were mostly mild to moderate, resolving within 3 days.The ALVAC-HIV and AIDSVAX B/E vaccine regimen was found to be safe, well tolerated and suitable for potential large-scale use in Thailand.ClinicalTrials.govNCT00223080

Systematic comparison of HIV-1 Envelope-specific IgG responses induced by different vaccination regimens: Can we steer IgG recognition towards regions of viral vulnerability?

Immunogens and vaccination regimens can influence patterns of immune-epitope recognition, steering them towards or away from epitopes of potential viral vulnerability. HIV-1 envelope (Env)-specific antibodies targeting variable region 2 (V2) or 3 (V3) correlated with protection during the RV144 trial, however, it was suggested that the immunodominant V3 region might divert antibody responses away from other relevant sites. We mapped IgG responses against linear Env epitopes in five clinical HIV vaccine trials, revealing a specific pattern of Env targeting for each regimen. Notable V2 responses were only induced in trials administering CRF01_AE based immunogens, but targeting of V3 was seen in all trials, with the soluble, trimeric CN54gp140 protein eliciting robust V3 recognition. Strong V3 targeting was linked to greater overall response, increased number of total recognised antigenic regions, and where present, stronger V2 recognition. Hence, strong induction of V3-specific antibodies did not negatively impact the targeting of other linear epitopes in this study, suggesting that the induction of antibodies against V3 and other regions of potential viral vulnerability need not be necessarily mutually exclusive

Comparison of the Single Cell Immune Landscape between Subjects with High <i>Mycobacterium tuberculosis</i> Bacillary Loads during Active Pulmonary Tuberculosis and Household Members with Latent Tuberculosis Infection

It is unclear how the immune system controls the transition from latent tuberculosis (TB) infection (LTBI) to active pulmonary infection (PTB). Here, we applied mass spectrometry cytometry time-of-flight (CyTOF) analysis of peripheral blood mononuclear cells to compare the immunological landscapes in patients with high tuberculous bacillary load PTB infections and LTBI. A total of 32 subjects (PTB [n = 12], LTBI [n = 17], healthy volunteers [n = 3]) were included. Participants with active PTBs were phlebotomized before administering antituberculosis treatment, whereas participants with LTBI progressed to PTB at the time of household screening. In the present study, CyTOF analysis identified significantly higher percentages of mucosal-associated invariant natural killer T (MAIT NKT) cells in subjects with LTBI than in those with active PTB and healthy controls. Moreover, 6 of 17 (35%) subjects with LTBI progressed to active PTB (LTBI progression) and had higher proportions of MAIT NKT cells and early NKT cells than those without progression (LTBI non-progression). Subjects with LTBI progression also showed a tendency toward low B cell levels relative to other subject groups. In conclusion, MAIT NKT cells were substantially more prevalent in subjects with LTBI, particularly those with progression to active PTB

International University Students’ Pre-Travel Preparation, Knowledge and Practices towards Travel Health in Thailand: A Nationwide Cross-Sectional Study

International university students are vulnerable travellers due to their unpredictable schedules and lifestyles. As Thailand continues to see an increase in international students, evaluating their pre-travel preparation and preventive behaviours is crucial to identify areas for improvement. For this purpose, an online survey focusing on pre-travel preparation, knowledge and preventive practices related to travel health was distributed to 324 eligible international students from 14 Thai universities, with the majority being from Asia and Oceania (79.0%; n = 256). The results showed that half of the respondents (53.7%; n = 175) received professional pre-travel advice, mainly because of the mandatory health examination and vaccination requirements of the host university. The study also revealed inadequate knowledge about infectious and non-infectious health risks, with only one-third being aware that Japanese encephalitis is transmitted by mosquito bites, and less than half of the students recognising Thailand’s emergency services number. Poor preventive practices were also observed, with less than half of those with new sexual partners consistently using condoms and less than half of those riding motorcycles always wearing helmets. These findings highlight the need for a new strategy to improve the standard of travel health preparation among this group of young adult travellers, particularly those from resource-limited countries

Predictors of postherpetic neuralgia in patients with herpes zoster: a pooled analysis of prospective cohort studies from North and Latin America and Asia

Objectives: The most common complication of herpes zoster (HZ) is postherpetic neuralgia (PHN), a persistent pain that can substantially affect quality of life (QoL). This analysis aimed to evaluate predictors of PHN in HZ patients. Methods: A pooled analysis of prospective cohort studies of HZ patients aged ≥50 years from North America (Canada), Latin America (Brazil, Mexico, and Argentina), and Asia (Taiwan, South Korea, and Thailand) was performed. Patients within 14 days of rash onset were included. The incidence of PHN was defined as a worst pain score of ≥3, persisting/appearing at >90 days after rash onset. Socio-demographics, HZ disease characteristics, treatment, pain-related interference with activities of daily living, and health-related QoL were assessed. Results: Of 702 patients with HZ, 148 (21.1%) developed PHN. Similar risks of PHN were observed across geographic regions. On multivariate analysis, older age, greater severity of pain at rash onset, employment status, walking problems at enrollment, and pain interference affecting social relationships were significantly associated with the development of PHN. Conclusions: In addition to older age and severe acute pain, this study suggests that impaired physical and social functioning from acute zoster pain may play a role in the development of PHN in this prospective cohort study of HZ patients from North and Latin America and Asia

Association between work time loss and quality of life in patients with Herpes Zoster: a pooled analysis of the MASTER studies

Background: Herpes zoster (HZ) has a significant negative effect on the productive work life of individuals, and has been shown to be responsible for cases of absenteeism, presenteeism and decreased work effectiveness. The aim of this study was to evaluate health utility scores and associated predictors in an actively employed population of Herpes Zoster (HZ) patients with and without work time loss (WTL). Methods: This was a pooled analysis of the prospective, observational MASTER cohort studies, conducted in 8 countries across North America, Latin America and Asia. A total of 428 HZ patients engaged in full or part time work were included. WTL, defined as missing ≥ 1 partial or full work day, and work effectiveness, reported on a scale of 0–100%, were evaluated with the Work and Productivity Questionnaire (WPQ). The Pearson product–moment correlation was used to assess the correlation between work effectiveness and HRQoL. Mixed models with repeated measures assessed the relationship between HZ-related WTL over a 6-month follow-up period, and HRQoL, as evaluated by the EQ-5D. Additional predictors of HRQoL were also identified. Results: Overall, 57.7% of respondents reported WTL. Mean (SD) percent work effectiveness of patients in the WTL group was significantly lower compared to non-WTL (NWTL) patients at baseline [50.3 (31.6) vs. 71.4 (27.8); p < 0.001]. Patients in the WTL group also reported lower health utility scores at baseline and overall than their NWTL counterparts, with WTL identified as an independent negative predictor of both the EQ-5D summary scores and the EQ-5D VAS (p < 0.001). Decrease in work effectiveness was negatively associated with HRQoL overall (p < 0.001). Predictors of lower HRQoL were worst Zoster Brief Pain Inventory (ZBPI) pain score, the presence of HZ complications and country income (predictor of EQ-5D VAS only). Conclusions: HZ adversely impacts the work and productive life of actively employed individuals. In turn, HZ-related reductions in work effectiveness and work time are associated with a negative effect on HRQoL. Electronic supplementary material The online version of this article (doi:10.1186/s12955-017-0588-x) contains supplementary material, which is available to authorized users

Antibody persistence 2 and 3 years after booster vaccination of adolescents with recombinant acellular pertussis monovalent aPgen or combined TdaPgen vaccines

BACKGROUND: Recombinant pertussis vaccines inducing long-lasting immune responses could help to control the rise in pertussis. We here report on persisting antibody responses 2 and 3 years after booster vaccination with a new generation recombinant acellular pertussis vaccine. METHODS: Participants of a phase 2/3 randomised-controlled clinical trial with a monovalent pertussis vaccine containing genetically inactivated pertussis toxin (aPgen) or its tetanus and diphtheria toxoids combination (TdaPgen), or a chemically detoxified comparator vaccine (Tdapchem), (originally conducted between July and August 2015) were invited to participate in observational studies of persisting antibody responses 2 and 3 years after vaccination. Serum IgG against pertussis toxin (PT-IgG) and filamentous hemagglutinin (FHA-IgG) were assessed by ELISA, and PT-neutralising antibodies (PT-Nab) by Chinese Hamster Ovary cell assay. FINDINGS: Waning of antibodies stabilised in aPgen and TdaPgen vaccinees 2 and 3 years after vaccination. Three years post-vaccination PT-neutralising antibodies remained 4·6-fold (95% Confidence Interval (CI) 2·6–8·1) and 3·7-fold (95% CI 2·2–6·1) higher, PT-IgG antibodies 3·0-fold (95% CI 2·2–4·1) and 2·5-fold (95% CI 1·9–3·3) higher, and FHA-IgG antibodies 1·8-fold (95% CI 1·3–2·5) and 1·6-fold (95% CI 1·2–2·1) higher than baseline in aPgen and TdaPgen recipients, respectively. In the Tdapchem group, PT-neutralising and PT-IgG and FHA-IgG antibodies were back at baseline levels 2 years post-vaccination. Three years post-vaccination seroconversion rates for PT-neutralising antibodies were 65·0% (95% CI 44·1–85·9) and 55·0% (95% CI 33·2–76·8) in aPgen and TdaPgen recipients, respectively. INTERPRETATION: Considering the persistence of elevated antibody responses 3 years post-booster vaccination, genetically detoxified monovalent aPgen and TdaPgen vaccines can be expected to induce longer-lasting protection than chemically inactivated Tdap vaccines