Serological Response to the 2009 Pandemic Influenza A (H1N1) Virus for Disease Diagnosis and Estimating the Infection Rate in Thai Population

BACKGROUND: Individuals infected with the 2009 pandemic virus A(H1N1) developed serological response which can be measured by hemagglutination-inhibition (HI) and microneutralization (microNT) assays. METHODOLOGY/PRINCIPAL FINDINGS: MicroNT and HI assays for specific antibody to the 2009 pandemic virus were conducted in serum samples collected at the end of the first epidemic wave from various groups of Thai people: laboratory confirmed cases, blood donors and health care workers (HCW) in Bangkok and neighboring province, general population in the North and the South, as well as archival sera collected at pre- and post-vaccination from vaccinees who received influenza vaccine of the 2006 season. This study demonstrated that goose erythrocytes yielded comparable HI antibody titer as compared to turkey erythrocytes. In contrast to the standard protocol, our investigation found out the necessity to eliminate nonspecific inhibitor present in the test sera by receptor destroying enzyme (RDE) prior to performing microNT assay. The investigation in pre-pandemic serum samples showed that HI antibody was more specific to the 2009 pandemic virus than NT antibody. Based on data from pre-pandemic sera together with those from the laboratory confirmed cases, HI antibody titers ≥ 40 for adults and ≥ 20 for children could be used as the cut-off level to differentiate between the individuals with or without past infection by the 2009 pandemic virus. CONCLUSIONS/SIGNIFICANCE: Based on the cut-off criteria, the infection rates of 7 and 12.8% were estimated in blood donors and HCW, respectively after the first wave of the 2009 influenza pandemic. Among general population, the infection rate of 58.6% was found in children versus 3.1% in adults

Long-term booster schedules with AS03A-adjuvanted heterologous H5N1 vaccines induces rapid and broad immune responses in Asian adults

BACKGROUND: The pandemic potential of avian influenza A/H5N1 should not be overlooked, and the continued development of vaccines against these highly pathogenic viruses is a public health priority. METHODS: This open-label extension booster study followed a Phase III study of 1206 adults who had received two 3.75 μg doses of primary AS03(A)-adjuvanted or non-adjuvanted H5N1 split-virus vaccine (A/Vietnam/1194/2004; clade 1) (NCT00449670). The aim of the extension study was to evaluate different timings for heterologous AS03(A)-adjuvanted booster vaccination (A/Indonesia/5/2005; clade 2.1) given at Month 6, 12, or 36 post-primary vaccination. Immunogenicity was assessed 21 days after each booster vaccination and the persistence of immune responses against the primary vaccine strain (A/Vietnam) and the booster strain (A/Indonesia) was evaluated up to Month 48 post-primary vaccination. Reactogenicity and safety were also assessed. RESULTS: After booster vaccination given at Month 6, HI antibody responses to primary vaccine, and booster vaccine strains were markedly higher with one dose of AS03(A)-H5N1 booster vaccine in the AS03(A)-adjuvanted primary vaccine group compared with two doses of booster vaccine in the non-adjuvanted primary vaccine group. HI antibody responses were robust against the primary and booster vaccine strains 21 days after boosting at Month 12 or 36. At Month 48, in subjects boosted at Month 6, 12, or 36, HI antibody titers of ≥1:40 against the booster strain persisted in 39.2%, 61.2%, and 95.6% of subjects, respectively. Neutralizing antibody responses and cell-mediated immune responses also showed that AS03(A)-H5N1 heterologous booster vaccination elicited robust immune responses within 21 days of boosting at Month 6, 12, or 36 post-primary vaccination. The booster vaccine was well tolerated, and no safety concerns were raised. CONCLUSIONS: In Asian adults primed with two doses of AS03(A)-adjuvanted H5N1 pandemic influenza vaccine, strong cross-clade anamnestic antibody responses were observed after one dose of AS03(A)-H5N1 heterologous booster vaccine given at Month 6, 12, or 36 after priming, suggesting that AS03(A)-adjuvanted H5N1 vaccines may provide highly flexible prime–boost schedules. Although immunogenicity decreased with time, vaccinated populations could potentially be protected for up to three years after vaccination, which is likely to far exceed the peak of the a pandemic

Risk behaviour and time as covariates for effi cacy of the HIV vaccine regimen ALVAC-HIV (vCP1521) and AIDSVAX B/E: a post-hoc analysis of the Thai phase 3 efficacy trial RV 144

Background The Thai phase 3 HIV vaccine trial RV 144 showed modest effi cacy of a vaccine against HIV acquisition. Baseline variables of age, sex, marital status, and risk did not modify vaccine effi cacy. We did a post-hoc analysis of the trial’s data to investigate behavioural risk and effi cacy every 6 months after vaccination. Methods RV 144 was a randomised, multicentre, double-blind, placebo-controlled effi cacy 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 modifi ed 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 classifi ed 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 eff ects 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 classifi ed as high or increasing risk at least once during followup 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 effi cacy was signifi cant (p=0·01), with greater benefi t in low-risk individuals. Vaccine effi cacy seemed to peak early—cumulative vaccine effi cacy 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 aff ect 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 eff ects. The regimen tested in the RV 144 phase 3 trial might benefi t 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

Estimation on the infection rates of the 2009 pandemic influenza in different groups of subjects after the first epide mic wave.

<p>Infection rate is determined by HI titer ≥40 in adults or ≥20 in children.</p

Subjects and time of specimen collection.

<p>Subjects and time of specimen collection.</p

Comparison between NT antibody titers obtained from RDE treated and RDE untreated sera.

<p>*There are significant differences between GMT of NT antibodies in RDE treated and untreated sera from all 7 serum settings (Wilcoxon Signed Ranks test, p<0.05).</p

Comparison between HI antibody titers obtained from goose and turkey erythrocytes.

<p>Note: A/Thailand/104/2009(H1N1) was used as the test virus. GMT  =  geometric mean titer, CI  =  confidence intervals, RBC  =  red blood cells,</p><p>NA  =  Not applicable</p

Antibody titers by date after onset of symptom.

<p>(A) HI antibody titer; (B) NT antibody titer. Colored stacked bars give the proportion with titers of 10, 20, 40 and ≥80 while the line denotes the geometric mean titer with error bars indicating 95% confidence intervals.</p