Limited data exist on the immunogenicity of the 2009 influenza A (H1N1) vaccine among immunocompromised persons, including those with human immunodeficiency virus (HIV) infection.We compared the immunogenicity and tolerability of a single dose of the monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009H1N1) between HIV-infected and HIV-uninfected adults 18-50 years of age. The primary end point was an antibody titer of ≥ 1:40 at day 28 after vaccination in those with a prevaccination level of ≤ 1:10, as measured by hemagglutination-inhibition assay. Geometric mean titers, influenza-like illnesses, and tolerability were also evaluated.One hundred thirty-one participants were evaluated (65 HIV-infected and 66 HIV-uninfected patients), with a median age of 35 years (interquartile range, 27-42 years). HIV-infected persons had a median CD4 cell count of 581 cells/mm(3) (interquartile range, 476-814 cells/mm(3)) , and 82% were receiving antiretroviral medications. At baseline, 35 patients (27%) had antibody titers of >1:10. HIV-infected patients (29 [56%] of 52), compared with HIV-uninfected persons (35 [80%] of 44), were significantly less likely to develop an antibody response (odds ratio, .20; P = .003). Changes in the median geometric mean titer from baseline to day 28 were also significantly lower in HIV-infected patients than in HIV-uninfected persons (75 vs 153; P = .001). Five influenza-like illnesses occurred (2 cases in HIV-infected persons), but none was attributable to the 2009 influenza H1N1 virus. The vaccine was well tolerated in both groups.Despite high CD4 cell counts and receipt of antiretroviral medications, HIV-infected adults generated significantly poorer antibody responses, compared with HIV-uninfected persons. Future studies evaluating a 2-dose series or more-immunogenic influenza A (H1N1) vaccines among HIV-infected adults are needed (ClinicalTrials.gov NCT00996970).
Dengue fever, caused by dengue viruses (DENV 1-4) is a leading cause of illness and death in the tropics and subtropics. Therefore, an effective vaccine is urgently needed. Currently, the only available licensed dengue vaccine is a chimeric live attenuated vaccine that shows varying efficacy depending on serotype, age and baseline DENV serostatus. Accordingly, a dengue vaccine that is effective in seronegative adults, children of all ages and in immunocompromised individuals is still needed. We are currently researching the use of psoralen to develop an inactivated tetravalent dengue vaccine. Unlike traditional formalin inactivation, psoralen inactivates pathogens at the nucleic acid level, potentially preserving envelope protein epitopes important for protective anti-dengue immune responses. We prepared highly purified monovalent vaccine lots of formalin- and psoralen-inactivated DENV 1-4, using Capto DeVirS and Capto Core 700 resin based column chromatography. Tetravalent psoralen-inactivated vaccines (PsIV) and formalin-inactivated vaccines (FIV) were prepared by combining the four monovalent vaccines. Mice were immunized with either a low or high dose of PsIV or FIV to evaluate the immunogenicity of monovalent as well as tetravalent formulations of each inactivation method. In general, the monovalent and tetravalent PsIVs elicited equivalent or higher titers of neutralizing antibodies to DENV than the FIV dengue vaccines and this response was dose dependent. The immunogenicity of tetravalent dengue PsIVs and FIVs were also evaluated in nonhuman primates (NHPs). Consistent with what was observed in mice, significantly higher neutralizing antibody titers for each dengue serotype were observed in the NHPs vaccinated with the tetravalent dengue PsIV compared to those vaccinated with the tetravalent dengue FIV, indicative of the importance of envelope protein epitope preservation during psoralen inactivation of DENV.
The emergence of avian influenza A/H5N1 in 2003 as well as the pandemic influenza A (H1N1) pdm09 highlighted the need to establish influenza sentinel surveillance in Togo. The Ministry of Health decided to introduce Influenza to the list of diseases with epidemic potential. By April 2010, Togo was actively involved in influenza surveillance. This study aims to describe the implementation of ILI surveillance and results obtained from April 2010 to December 2012. Two sites were selected based on their accessibility and affordability to patients, their adequate specimen storage capacity and transportation system. Patients with ILI presenting at sentinel sites were enrolled by trained medical staff based on the World Health Organization (WHO) case definitions. Oropharyngeal and nasopharyngeal samples were collected and they were tested at the National Influenza Reference Laboratory using a U.S. Centers for Disease Control and Prevention (CDC) validated real time RT-PCR protocol. Laboratory results and epidemiological data were reported weekly and shared with all sentinel sites, Ministry of Health, Division of Epidemiology, WHO and CDC/NAMRU-3. From April 2010 to December 2012, a total of 955 samples were collected with 52% of the study population aged between 0 and 4 years. Of the 955 samples, 236 (24.7%) tested positive for influenza viruses; with 136 (14.2%) positive for influenza A and 100 (10.5%) positive for influenza B. The highest influenza positive percentage (30%) was observed in 5–14 years old and patients aged 0–4 and >60 years had the lowest percentage (20%). Clinical symptoms such as cough and rhinorrhea were associated more with ILI patients who were positive for influenza type A than influenza type B. Influenza viruses circulated throughout the year with the positivity rate peaking around the months of January, May and again in October; corresponding respectively to the dry-dusty harmattan season and the long and then the short raining season. The pandemic A (H1N1) pdm09 was the predominantly circulating strain in 2010 while influenza B was the predominantly circulating strain in 2011. The seasonal A/H3N2 was observed throughout 2012 year. This study provides information on influenza epidemiology in the capital city of Togo.
Abstract Reliable detection and diagnosis of dengue virus (DENV) is important for both patient care and epidemiological control. Starting with a llama immunized with a mixture of recombinant nonstructural protein 1 (NS1) antigen from the four DENV serotypes, a phage display immune library of single domain antibodies was constructed and binders selected which exhibited specificity and affinity for DENV NS1. Each of these single domain antibodies was evaluated for its binding affinity to NS1 from the four serotypes, and incorporated into a sandwich format for NS1 detection. An optimal pair was chosen that provided the best combination of sensitivity for all four DENV NS1 antigens spiked into 50% human serum while showing no cross reactivity to NS1 from Zika virus, yellow fever virus, tick-borne encephalitis virus, and minimal binding to NS1 from Japanese encephalitis virus and West Nile virus. These rugged and robust recombinant binding molecules offer attractive alternatives to conventional antibodies for implementation into immunoassays destined for resource limited locals.
Dengue vascular permeability syndrome is the primary cause of death in severe dengue infections. The protective versus potentially pathogenic role of dengue NS1 antibodies are not well understood. The main goal of this analysis was to characterize the relationship between free NS1 concentration and NS1 antibody titers in primary and secondary dengue infection in order to better understand the presence and duration of NS1 antibody complexes in clinical dengue infections.
Abstract Antibody (Ab)-dependent enhancement (ADE) is a hypothesized mechanism of increased disease severity during secondary dengue virus (DENV) infection. This study investigates Ab-dependent cell cytotoxicity (ADCC) in counteracting ADE. In our system, DENV and DENV-immune sera were added to peripheral blood mononuclear cells (PBMCs), and ADE and NK cell activation were simultaneously monitored. ADE was detected in monocytes and a concurrent activation of NK cells was observed. Activated NK cells expressed IFN-γ and CD107a. IFN-γ was detected at 24 hours (24 h) followed by a rapid decline; CD107a expression peaked at 48 h and persisted for >7 days. Optimal activation of NK cells required the presence of enhancement serum together with ADE-affected monocytes and soluble factors, suggesting the coexistence of the counteractive ADCC Abs, in the same ADE-serum, capable of strongly promoting NK cell activation. The function of NK cells against ADE was demonstrated using a depletion assay. NK cell-depleted PBMCs had increased ADE as compared to whole PBMCs. Conversely, adding activated NK cells back into the NK-depleted-PBMCs or to purified monocytes decreased ADE. Blocking IFN-γ expression also increased ADE. The study suggests that under ADE conditions, NK cells can be activated by ADCC Abs and can control the magnitude of ADE.
