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• One of the biggest challenges for global health vaccines has been access to the people who need them. • Developing country vaccine manufacturers play an essential role in vaccine supply worldwide. • Improvement of supply chain and innovative delivery methods lead to increased vaccine coverage. • The COVID-19 pandemic impacts the delivery of health services, including immunizations, in LMICs. • The distribution, and critically the equitable distribution, of COVID-19 vaccines will be a daunting task of unprecedented magnitude and scale. Vaccines developed in high-income countries have been enormously successful in reducing the global burden of infectious diseases, saving perhaps 2.5 million lives per year, but even for successful cases, like the rotavirus vaccine, global implementation may take a decade or more. For unincentivized vaccines, the delays are even more profound, as both the supply of a vaccine from developing country manufacturers and vaccine demand from countries with the high disease burdens have to be generated in order for impact to be manifest. A number of poverty-associated infectious diseases, whose burden is greatest in low-income and middle-income countries, would benefit from appropriate levels of support for vaccine development such as Group A Streptococcus, invasive non-typhoid salmonella, schistosomiasis, shigella, to name a few. With COVID-19 vaccines we will hopefully be able to provide novel vaccine technology to all countries through a unique collaborative effort, the COVAX facility, led by the World Health Organization (WHO), Gavi, and the Coalition for Epidemic Preparedness Innovations (CEPI). Whether this effort can deliver vaccine to all its participating countries remains to be seen, but this ambitious effort to develop, manufacture, distribute, and vaccinate 60–80% of the world's population will hopefully be a lasting legacy of COVID-19. [ABSTRACT FROM AUTHOR]

The current global initiative to end Cholera by 2030 emphasizes the use of oral cholera vaccine (OCV) combined with feasible household Water-Sanitation-Hygiene (WASH) interventions. However, little is known about how improved WASH practices and behaviors and OCV interact to reduce the risk of cholera. We reanalyzed two arms of a cluster-randomized trial in urban Bangladesh, to evaluate the effectiveness of OCV given as a 2-dose regimen. One arm (30 clusters, n = 94,675) was randomized to vaccination of persons aged one year and older with OCV, and the other arm (30 clusters, n = 80,056) to no intervention. We evaluated the prevention of cholera by household WASH, classified at baseline using a previously validated rule, and OCV over 2 years of follow-up. When analyzed by assignment to OCV clusters rather than receipt of OCV, in comparison to persons living in "Not Better WASH" households in the control clusters, reduction of severe cholera (the primary outcome) was similar for persons in "Not Better WASH" households in vaccine clusters (46%, 95% CI:24,62), for persons in "Better WASH" households in the control clusters (48%, 95% CI:25,64), and for persons in "Better WASH" households in the vaccine clusters (48%, 95% CI:16,67). In contrast, when analyzed by actual receipt of a complete OCV regimen, , in comparison to persons in "Not Better WASH" households in the control clusters, protection against severe cholera increased steadily from 39% (95% CI:13,58) in residents of "Better WASH" households in the control clusters to 57% (95% CI:35,72) in vaccinated persons in "Not Better WASH" households to 63% (95% CI:21,83) in vaccinated persons in "Better WASH" households. This analysis suggests that improved household WASH and OCV received may interact to provide greater protection against cholera. However, the divergence between findings related to intent to vaccinate versus those pertaining to actual receipt of OCV underscores the need for further research on this topic. [ABSTRACT FROM AUTHOR]

Chikungunya is a neglected tropical disease of growing public health concern with outbreaks in more than 114 countries in Asia, Africa, Americas, Europe, and Oceania since 2004. There are no specific antiviral treatment options for chikungunya virus infection. This article describes the chikungunya vaccine pipeline and assesses the challenges in the path to licensure, access, and uptake of chikungunya vaccines in populations at risk. Ixchiq (VLA1533/Ixchiq – Valneva) was the first licensed chikungunya vaccine by the US Food and Drug Administration in November 2023, European Medicines Agency in May 2024, and Health Canada in June 2024. Five chikungunya vaccine candidates (BBV87 – BBIL/IVI, MV-CHIK – Themis Bioscience, ChAdOx1 Chik – University of Oxford, PXVX0317 / VRC-CHKVLP059–00-VP – Bavarian Nordic, and mRNA-1388 – Moderna) are in development. Evidence on chikungunya disease burden alongside the public health and economic impact of vaccination are critical for decision-making on chikungunya vaccine introduction in endemic and epidemic settings. Further, global and regional stakeholders need to agree on a sustainable financing mechanism for manufacturing at scale to facilitate fair access and equitable vaccine distribution to at-risk populations in different geographic settings. This could partly be facilitated through obtaining consensus on scientific and regulatory principles for initial vaccine introduction and generating evidence on chikungunya burden and disease awareness among populations at risk. Specifically, this article advocates for the formation of a global chikungunya vaccine consortium that includes regulators, policymakers, sponsors, and manufacturers to assist in overcoming the global and local challenges for chikungunya vaccine licensure, policy, financing, demand generation, and access to at-risk populations. [ABSTRACT FROM AUTHOR]

• Vi-DT with or without MMR is safe and well tolerated in infants aged 9–15 months. • Study demonstrated Immune non-interference of MMR vaccine to Vi-DT conjugate vaccine and vice versa. • Vi-DT could be considered as an addition to the EPI schedule among children at risk of contracting typhoid fever. Typhoid fever is a common disease in developing countries especially in the Indian subcontinent and Africa. The available typhoid conjugate vaccines (TCV) have been found to be highly immunogenic in infants and children less than 2 years of age. Many countries are planning to adopt TCV in their routine EPI programs around 9 months of age when measles containing vaccines are given. Therefore, Vi-DT TCV was tested in 9–15 months aged healthy infants in Nepal to demonstrate non-interference with a measles containing vaccine. This was a randomized, open label, phase III study to assess the immune non-interference, safety, and reactogenicity of Vi-DT typhoid conjugate vaccine when given concomitantly with measles, mumps and rubella (MMR) vaccine. A total of 360 participants aged 9–15 months were enrolled and randomized equally into Vi-DT + MMR (180 participants) or MMR alone (180 participants) group and were evaluated for immunogenicity and safety 28 days post vaccination. Using the immunogenicity set, difference between proportions (95% CI) of the Vi-DT + MMR group vs MMR alone group were −2.73% (-8.85, 3.38), −3.19% (-11.25, 4.88) and 2.91% (-3.36, 9.18) for sero-positivity rate of anti-measles, anti-mumps and anti- rubella, respectively. Only the lower bound of the range in difference of the proportions for sero-positivity rate of anti-mumps did not satisfy the non-inferiority criteria as it was above the −10% limit, which may not be of clinical significance. These results were confirmed in the per protocol set. There were no safety concerns reported from the study and both Vi-DT + MMR and MMR alone groups were comparable in terms of solicited and unsolicited adverse events. Results indicated that there is non-interference of MMR vaccine with Vi-DT and Vi-DT conjugate vaccine could be considered as an addition to the EPI schedule among children at risk of contracting typhoid. [ABSTRACT FROM AUTHOR]

Background: Killed whole-cell oral cholera vaccines (OCVs) are widely used for prevention of cholera in developing countries. However, few studies have evaluated the protection conferred by internationally recommended OCVs for durations beyond 2 years of follow-up.Methods: In this study, we followed up the participants of a cluster-randomised controlled trial for 2 years after the end of the original trial. Originally, we had randomised 90 geographical clusters in Dhaka slums in Bangladesh in equal numbers (1:1:1) to a two-dose regimen of OCV alone (targeted to people aged 1 year or older), a two-dose regimen of OCV plus a water-sanitation-hygiene (WASH) intervention, or no intervention. There was no masking of group assignment. The WASH intervention conferred little additional protection to OCV and was discontinued at 2 years of follow-up. Surveillance for severe cholera was continued for 4 years. Because of the short duration and effect of the WASH intervention, we combined the two OCV intervention groups. The primary outcomes were OCV overall protection (protection of all members of the intervention clusters) and total protection (protection of individuals who got vaccinated in the intervention clusters) against severe cholera, which we assessed by multivariable survival models appropriate for cluster-randomised trials. This trial is registered on ClinicalTrials.gov, NCT01339845.Findings: The study was done between April 17, 2011, and Nov 1, 2015. 268 896 participants were present at the time of the first dose, with 188 206 in the intervention group and 80 690 in the control group. OCV coverage of the two groups receiving OCV was 66% (123 659 of 187 214 participants). During 4 years of follow-up, 441 first episodes of severe cholera were detected (243 episodes in the vaccinated groups and as 198 episodes in the unvaccinated group). Overall OCV protection was 36% (95% CI 19 to 49%) and total OCV protection was 46% (95% CI 32 to 58). Cumulative total vaccine protection was notably lower for people vaccinated before the age of 5 years (24%; -30 to 56) than for people vaccinated at age 5 years or older (49%; 35 to 60), although the differences in protection for the two age groups were not significant (p=0·3308). Total vaccine protection dropped notably (p=0·0115) after 3 years in children vaccinated at 1-4 years of age.Interpretation: These findings provide further evidence of long-term effectiveness of killed whole-cell OCV, and therefore further support for the use of killed whole-cell OCVs to control endemic cholera, but indicate that protection is shorter-lived in children vaccinated before the age of 5 years than in people vaccinated at the age of 5 years or older.Funding: Bill & Melinda Gates Foundation.Translation: For the Bengali translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

• The "fried-egg" analytic approach was applied to a cluster randomized trial (CRT). • Overall analysis failed to reveal rotavirus vaccine (RV) herd protection. • Same approach unmasked herd protection of other enteric vaccines failed for RV. Vaccine herd protection assessed in a cluster-randomized trial (CRT) may be masked by disease transmission into the cluster from outside. However, herd effects can be unmasked using a 'fried-egg' approach whereby the analysis, restricted to the innermost households of clusters, 'yolk', creates an insulating 'egg-white' periphery. This approach has been demonstrated to unmask vaccine herd protection in reanalyses of cholera and typhoid vaccine CRTs. We applied this approach to an earlier CRT in Bangladesh of rotavirus vaccine (RV) whose overall analysis had failed to detect herd protection. Herein we present the results of this analysis. In the study area, infants in 142 villages were randomized to receive two doses of RV with routine EPI vaccines (RV villages) or only EPI vaccines (non-RV villages). We analyzed RV protection against acute rotavirus diarrhoea for the entire cluster (P100) and P75, P50, P25 clusters, representing 75%, 50% and 25% of the innermost households for each cluster, respectively. During 2 years of follow-up, there was evidence of 27% overall (95 %CI: 7, 43) and 42% total protection (95 %CI: 23, 56) in the P100 cluster, but it did not increase when moved in smaller yolks. There was no evidence of indirect vaccine protection in the yolks at any cluster size. Our reanalysis of the CRT using the fried- egg approach did not detect RV herd protection. Whether these findings reflect a true inability of the RV to confer herd protection in this setting, or are due to limitations of the approach, requires further study. [ABSTRACT FROM AUTHOR]

• Vi-DT is safe and well tolerated in infants and toddlers aged 6–23 months. • Vi-DT showed >1000-fold higher Geometric Mean Titer (GMT) compared to Placebo. • 100% seroconversion reported in Vi-DT group in all age strata. Typhoid fever remains an important public health problem in developing countries and is endemic in many parts of Asia and Africa where the incidence of disease typically peaks in school-aged children. Age restrictions and other limitations of existing oral live-attenuated typhoid and parenteral Vi polysaccharide vaccines have triggered the development of Vi conjugate vaccines with improved immunological properties, use in younger age range, and longer durability of protection. We present the safety, reactogenicity, and immunogenicity data from a Phase II study after a single dose of Vi polysaccharide conjugated to diphtheria toxoid (Vi-DT) conducted in 6–23-month old Filipino children. This is a randomized, observer-blinded Phase II study to assess the immunogenicity, safety and reactogenicity of Vi-DT compared to placebo, conducted in Muntinlupa City, The Philippines. Participants aged 6–23 months were enrolled and randomized to Vi-DT (25 µg) or placebo (0.9% sodium chloride) and evaluated for immunogenicity and overall safety 28 days post vaccination. A total of 285 participants were enrolled and age-stratified: 6 to < 9 months, 9–12 months, and 13–23 months. Seventy-six (76) participants received Vi-DT and 19 received placebo per each strata. All participants seroconverted after a single dose of Vi-DT versus 7% of placebo recipients. Anti-Vi IgG GMT was 444.38 [95% CI (400.28; 493.34)] after a single dose of Vi-DT; there was no change in GMT after placebo administration, 0.41 [95% CI (0.33; 0.51), p < 0.0001]. A similar pattern of immunogenicity was reported across all age strata. The vaccine reported to be safe and well tolerated. Vi-DT vaccine was immunogenic, safe, and well tolerated in children aged 6–23 months. ClinicalTrials.gov registration number: NCT03527355. [ABSTRACT FROM AUTHOR]

We have earlier reported that a single dose of oral cholera vaccine (OCV) is protective in adults and children ≥5 years of age and sustained for 2 years. We enrolled participants (n = 240) from this study, between March-September 2017, over 3 years after receiving a primary single dose. Immune responses were measured in placebo group (Primary Immunization group: PI) and compared with those who received a single dose (Booster Immunization group: BI). The children were 4 to <5 years, 5 to <18 years and adults >18 years. Blood was collected at day 0 (before vaccination) and after receiving 1st and 2nd doses of OCV. Overall, the BI and PI groups showed vibriocidal antibody response after 1st and 2nd dose of vaccination in all age groups to V. cholerae O1 and O139. Young children in the BI group showed significantly higher vibriocidal antibody response two weeks after receiving the first dose as compared to PI group to LPS. Elevated plasma IgA responses to LPS after the first dose were observed among the BI group compared to the PI group among the young children. Mucosal antibody responses measured in fecal extracts showed similar increases as that of vibriocidal and LPS responses in the BI group. These results suggest a single boosting dose of OCV generated immune response in primed population >5 years of age who had earlier received OCV. However, young children who had received OCV earlier, boosting after a single dose, resulted in increased immune responses compared to the PI group. Further studies are needed to assess protection obtained from different strategies, especially for young children and to determine the numbers of primary and booster doses needed. In addition, more information is needed regarding the optimum interval between primary and booster doses to plan future interventions for cholera control. ClinicalTrials.gov Identifier: NCT 02027207. [ABSTRACT FROM AUTHOR]

Emerging and re-emerging infectious diseases are an expanding global threat to public health, security, and economies. Increasing populations, urbanization, deforestation, climate change, anti-vaccination movements, war, and international travel are some of the contributing factors to this trend. The recent Ebola, MERS-CoV, and Zika outbreaks demonstrated we are insufficiently prepared to respond with proven safe and effective countermeasures (i.e., vaccines and therapeutics). The State University of New York Upstate Medical University and the Trudeau Institute convened a summit of key opinion and thought leaders in the life sciences and biomedical research and development enterprises to explore global biopreparedness challenges, take an inventory of existing capabilities and capacities related to preparation and response, assess current "gaps," and prospect what could be done to improve our position. Herein we describe the summit proceedings, "Translational Immunology Supporting Biomedical Countermeasure Development for Emerging Vector-borne Viral Diseases," held October 2–3, 2018, at the Trudeau Institute in Saranac Lake, NY. [ABSTRACT FROM AUTHOR]

Abstract Cholera, a diarrheal disease primarily affecting vulnerable populations in developing countries, is estimated to cause disease in more than 2.5 million people and kill almost 100,000 annually. An oral cholera vaccine (OCV) has been available globally since 2001; the demand for this vaccine from affected countries has however been very low, due to various factors including vaccine price and mode of administration. The low demand for the vaccine and limited commercial incentives to invest in research and development of vaccines for developing country markets has kept the global supply of OCVs down. Since 1999, the International Vaccine Institute has been committed to make safe, effective and affordable OCVs accessible. Through a variety of partnerships with collaborators in Sweden, Vietnam, India and South Korea, and with public and private funding, IVI facilitated development and production of two affordable and WHO-prequalified OCVs and together with other stakeholders accelerated the introduction of these vaccines for the global public-sector market. [ABSTRACT FROM AUTHOR]

While progress towards a Group A Streptococcus (GAS) vaccine has been stalled by a combination of scientific, regulatory, and commercial barriers, the problem persists. The high and globally-distributed burden of disease attributable to GAS makes vaccination an imperative global public health goal. Advances across a range of scientific disciplines in understanding GAS diseases have made the goal a realistic one and focused attention on the need for coordinated global action. With a view to accelerating GAS vaccine development, the World Health Organization (WHO) and the International Vaccine Institute (IVI) convened a global stakeholder consultation on the 12th and 13th of December 2016, in Seoul, South Korea. Topics discussed included: (1) gaps in current knowledge of global GAS epidemiology, burden of disease, and molecular epidemiology; (2) contribution of pre-clinical models to candidate vaccine evaluation and new immunological assays to address GAS immunology knowledge gaps; (3) status and future of the GAS vaccine development pipeline; and (4) defining a pathway to licensure, policy recommendations and availability of a vaccine. The meeting determined to establish a GAS vaccine working group to coordinate preparation of a global vaccine values proposition, preferred product characteristics, and a technical research and development roadmap. A new global GAS vaccine consortium will drive strategic planning to anticipate requirements for licensure, prequalification, and policy recommendations. [ABSTRACT FROM AUTHOR]

Background The evaluation of durable immune responses is important in HIV vaccine research and development. The efficiency of such evaluation could be increased by incorporating predictors of the responses in the statistical analysis. In this paper, we investigated whether and how baseline demographic variables and immune responses measured two weeks after vaccination predicted durable immune responses measured six months later. Methods We included data from seven preventive HIV vaccine regimens evaluated in three clinical trials: a Phase 1 study of four DNA, NYVAC and/or AIDSVAX vaccine regimens (HVTN096), a Phase 2 study of two DNA and/or MVA vaccine regimens (HVTN205), and a Phase 3 study of a single ALVAC/AIDSVAX regimen (RV144). Regularized random forests and linear regression models were used to identify and evaluate predictors of the positivity and magnitude of durable immune responses. Results We analyzed 201 vaccine recipients with data from 10 to 127 immune response biomarkers, and 3–5 demographic variables. The best prediction of participants’ durable response positivity based on two-week responses rendered up to close-to-perfect accuracy; the best prediction of participants’ durable response magnitude rendered correlation coefficients between the observed and predicted responses ranging up to 0.91. Though prediction performances differed among biomarkers, durable immune responses were best predicted by the two-week response level of the same biomarker. Adding demographic information and two-week response levels of different biomarkers provided little or no improvement in the predictions. Conclusions For some biomarkers and for the vaccines we studied, two-week post-vaccination responses can well predict durable responses six months later. Therefore, if immune response durability is only assessed in a sub-sample of vaccine recipients, statistical analyses of durable responses will have increased efficiency by incorporating two-week response data. Further research is needed to generalize the findings to other vaccine regimens and biomarkers. Clinicaltrials.gov identifiers: NCT01799954 , NCT00820846 , NCT00223080 . [ABSTRACT FROM AUTHOR]

A globally effective vaccine strategy must cope with the broad genetic diversity of HIV and contend with multiple transmission modalities. Understanding correlates of protection and the role of diversity in limiting protective vaccines with those correlates is key. RV144 was the first HIV-1 vaccine trial to demonstrate efficacy against HIV-1 infection. A correlates analysis comparing vaccine-induced immune responses in vaccinated-infected and vaccinated-uninfected volunteers suggested that IgG specific for the V1V2 region of gp120 was associated with reduced risk of HIV-1 infection and that plasma Env IgA was directly correlated with infection risk. RV144 and recent non-human primate (NHP) challenge studies suggest that Env is essential and perhaps sufficient to induce protective antibody responses against mucosally acquired HIV-1. Whether RV144 immune correlates can apply to different HIV vaccines, to populations with different modes and intensity of transmission, or to divergent HIV-1 subtypes remains unknown. Newer prime-boost mosaic and conserved sequence immunization strategies aiming at inducing immune responses of greater breadth and depth as well as the development of immunogens inducing broadly neutralizing antibodies should be actively pursued. Efficacy trials are now planned in heterosexual populations in southern Africa and men who have sex with men in Thailand. Although NHP challenge studies may guide vaccine development, human efficacy trials remain key to answer the critical questions leading to the development of a global HIV-1 vaccine for licensure. [ABSTRACT FROM AUTHOR]

Highlights: [•] The amino acid characteristics of HIV-1-Gag-p24 proteasomal peptides were determined. [•] Peptides with flanking regions were designed to generate CTL-epitopes. [•] Proteasomal degradation of the designed peptides generated CD8+ CTL epitopes. [•] The designed peptides induced IFN-γ from CD8+ CTL epitope-specific cells. [ABSTRACT FROM AUTHOR]

Summary: Background: The Thai phase 3 HIV vaccine trial RV 144 showed modest efficacy of a vaccine against HIV acquisition. Baseline variables of age, sex, marital status, and risk did not modify vaccine efficacy. We did a post-hoc analysis of the trial''s data to investigate behavioural risk and efficacy every 6 months after vaccination. Methods: RV 144 was a randomised, multicentre, double-blind, placebo-controlled efficacy trial testing the combination of the HIV vaccines ALVAC-HIV (vCP1521) and AIDSVAX B/E to prevent HIV infection or reduce setpoint viral load. Male and female volunteers aged 18–30 years were recruited from the community. In this post-hoc analysis of the modified intention-to-treat population (16 395 participants), HIV risk behaviour was assessed with a self-administered questionnaire at the time of initial vaccination in the trial and every 6 months thereafter for 3 years. We classified participants'' behaviour as low, medium, or high risk. Both the acquisition endpoint and the early viral-load endpoint were examined for interactions with risk status over time and temporal effects after vaccination. Multiple proportional hazards regression models with treatment and time-varying risk covariates were analysed. Findings: Risk of acquisition of HIV was low in each risk group, but 9187 (58·2%) participants reported higher-risk behaviour at least once during the study. Participants classified as high or increasing risk at least once during follow-up were compared with those who maintained low-risk or medium-risk behaviour as a time-varying covariate, and the interaction of risk status and acquisition efficacy was significant (p=0·01), with greater benefit in low-risk individuals. Vaccine efficacy seemed to peak early—cumulative vaccine efficacy was estimated to be 60·5% (95% CI 22–80) through the 12 months after initial vaccination—and declined quickly. Vaccination did not seem to affect viral load in either early or late infections. Interpretation: Future HIV vaccine trials should recognise potential interactions between challenge intensity and risk heterogeneity in both population and treatment effects. The regimen tested in the RV 144 phase 3 trial might benefit from extended immunisation schedules. Funding: US Army Medical Research and Materiel Command and Division of AIDS, National Institute of Allergy and Infectious Disease, National Institutes of Health. [Copyright &y& Elsevier]

Abstract: The current study assessed the immunogenicity and protective efficacy of various prime-boost vaccine regimens in rhesus macaques using combinations of recombinant DNA (rDNA), recombinant MVA (rMVA), and subunit gp140 protein. The rDNA and rMVA vectors were constructed to express Env from HIV-1 subtype CRF01_AE and Gag-Pol from CRF01_AE or SIVmac 239. One of the rMVAs, MVA/CMDR, has been recently tested in humans. Immunizations were administered at months 0 and 1 (prime) and months 3 and 6 (boost). After priming, HIV env-specific serum IgG was detected in monkeys receiving gp140 alone or rMVA but not in those receiving rDNA. Titers were enhanced in these groups after boosting either with gp140 alone or with rMVA plus gp140. The groups that received the rDNA prime developed env-specific IgG after boosting with rMVA with or without gp140. HIV Env-specific serum IgG binding antibodies were elicited more frequently and of higher titer, and breadth of neutralizing antibodies was increased with the inclusion of the subunit Env boost. T cell responses were measured by tetramer binding to Gag p11c in Mamu-A*01 macaques, and by IFN-γ ELISPOT assay to SIV-Gag. T cell responses were induced after vaccination with the highest responses seen in macaques immunized with rDNA and rMVA. Macaques were challenged intravenously with a novel SHIV-E virus (SIVmac239 Gag-Pol with an HIV-1 subtype E-Env CAR402). Post challenge with SHIV-E, antibody titers were boosted in all groups and peaked at 4 weeks. Robust T cell responses were seen in all groups post challenge and in macaques immunized with rDNA and rMVA a clear boosting of responses was seen. A greater than two-log drop in RNA copies/ml at peak viremia and earlier set point was achieved in macaques primed with rDNA, and boosted with rMVA/SHIV-AE plus gp140. Post challenge viremia in macaques immunized with other regimens was not significantly different to that of controls. These results demonstrate that a gp140 subunit and inclusion of SIV Gag-Pol may be critical for control of SHIV post challenge. [Copyright &y& Elsevier]

Abstract: Immune responses to vaccines may be influenced or associated with allelic variants of host genes such as those encoding human leucocyte antigens (HLA). We have molecularly determined the HLA class II DR and DQ gene, allele and haploype profiles in HIV-1 negative ethnic Thai recipients of an HIV-1 prime boost vaccine regimen, designed to induce neutralizing antibody (NAb) responses to HIV-1 CRF01_AE. Non-response to vaccine associated with DRB1*11 (3/32 responders vs. 7/13 non-responders, p c =0.027) and DRB1*16:02 (0/32 responders vs. 4/13 non-responders, p c =0.078) alleles. Furthermore, vaccine recipients with HLA-DQ heterodimers encoded by DQA1*05:01 and DQB1*03:01 alleles, were much less likely to produce NAb (p =0.009). These data suggest that the lack of response to a vaccine designed to induce clade-specific NAb to HIV-1 is associated with the presence of certain HLA class II alleles and heterodimers in some Southeast Asians. [Copyright &y& Elsevier]

Summary: Objectives: To assess differences between injecting drug users (IDUs) with hepatitis C virus (HCV) viremia and IDUs with HCV antibody (Ab) or no evidence of prior infection in three Afghan cities. Methods: IDUs in Hirat, Jalalabad, and Mazar-i-Sharif completed questionnaires and rapid testing for blood-borne infections including HCV Ab. HCV Ab was confirmed with a recombinant immunoblot assay (RIBA); RIBA-positive specimens underwent reverse transcriptase polymerase chain reaction (RT-PCR) for HCV. Risk behaviors associated with viremia were assessed with site-controlled ordinal regression analysis. Results: Of 609 participants, 223 (36.6%) had confirmed HCV Ab. Of 221 with serum available for PCR evaluation, 127 (57.5%) were viremic. HCV viremia prevalence did not differ by site (range 41.7–59.1%; p =0.52). Among all IDUs, in age and site-controlled ordinal regression analysis, HCV was independently associated with HIV co-infection (adjusted odds ratio (AOR) 7.16, 95% confidence interval (CI) 4.41–11.64), prior addiction treatment (AOR 1.95, 95% CI 1.57–2.42), ever aspirating and re-injecting blood (AOR 1.62, 95% CI 1.18–2.23), prior incarceration (AOR 1.60, 95% CI 1.04–2.45), and sharing injecting equipment in the last 6 months (AOR 1.35, 95% CI 1.02–1.80). Conclusion: HCV viremia was present in many participants with prior HCV infection and was associated with some injecting risk behaviors, indicating a substantial risk for transmission. Current harm reduction programs should aim to improve HCV awareness and prevention among IDUs in Afghanistan as a matter of urgency. [ABSTRACT FROM AUTHOR]