Long-term antibody persistence after vaccination with a 2-dose Havrix™ (inactivated hepatitis A vaccine): 20 years of observed data, and long-term model-based predictions

AbstractAntibody persistence in two cohorts of adults, who received inactivated hepatitis A (HAV) vaccine (1440El.U; Havrix™; GSK Vaccines) according to a 0–6 or 0–12 month schedule in 1992–1993, has been measured annually. After 20 years, >97% of the subjects in both studies were seropositive for anti-HAV antibodies. Geometric mean concentrations in the according-to-protocol cohorts were 312mIU/ml in 34/36 subjects vaccinated initially at 0–6 months (NCT00289757) and 317mIU/ml in 85/86 subjects vaccinated at 0–12 months (NCT00291876). Over the whole follow-up period, seven subjects (2+5, respectively) lost circulating anti-HAV antibodies but mounted a strong response after HAV booster administration (1440El.U). Mathematical modelling, which was applied to assess true persistence at Year 20 (accounting for drop-outs and missing data), and to predict longer-term persistence confirmed previous estimates that seropositive anti-HAV levels would persist in ≥95% vaccinees at Year 30 and ≥90% at Year 40.ClinicalTrials.Gov number: NCT00289757/NCT0029187

Phase 2b Controlled Trial of M72/AS01E Vaccine to Prevent Tuberculosis.

BACKGROUND: A vaccine to interrupt the transmission of tuberculosis is needed. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2b trial of the M72/AS01E tuberculosis vaccine in Kenya, South Africa, and Zambia. Human immunodeficiency virus (HIV)-negative adults 18 to 50 years of age with latent M. tuberculosis infection (by interferon-γ release assay) were randomly assigned (in a 1:1 ratio) to receive two doses of either M72/AS01E or placebo intramuscularly 1 month apart. Most participants had previously received the bacille Calmette-Guérin vaccine. We assessed the safety of M72/AS01E and its efficacy against progression to bacteriologically confirmed active pulmonary tuberculosis disease. Clinical suspicion of tuberculosis was confirmed with sputum by means of a polymerase-chain-reaction test, mycobacterial culture, or both. RESULTS: We report the primary analysis (conducted after a mean of 2.3 years of follow-up) of the ongoing trial. A total of 1786 participants received M72/AS01E and 1787 received placebo, and 1623 and 1660 participants in the respective groups were included in the according-to-protocol efficacy cohort. A total of 10 participants in the M72/AS01E group met the primary case definition (bacteriologically confirmed active pulmonary tuberculosis, with confirmation before treatment), as compared with 22 participants in the placebo group (incidence, 0.3 cases vs. 0.6 cases per 100 person-years). The vaccine efficacy was 54.0% (90% confidence interval [CI], 13.9 to 75.4; 95% CI, 2.9 to 78.2; P=0.04). Results for the total vaccinated efficacy cohort were similar (vaccine efficacy, 57.0%; 90% CI, 19.9 to 76.9; 95% CI, 9.7 to 79.5; P=0.03). There were more unsolicited reports of adverse events in the M72/AS01E group (67.4%) than in the placebo group (45.4%) within 30 days after injection, with the difference attributed mainly to injection-site reactions and influenza-like symptoms. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups. CONCLUSIONS: M72/AS01E provided 54.0% protection for M. tuberculosis-infected adults against active pulmonary tuberculosis disease, without evident safety concerns. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598 .)

Vaccine efficacy of ALVAC-HIV and bivalent subtype C gp120–MF59 in adults

BACKGROUND : A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox–protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1–2a trial in South Africa. Efficacy data and additional safety data were needed for this regimen in a larger population in South Africa. METHODS : In this phase 2b–3 trial, we randomly assigned 5404 adults without HIV-1 infection to receive the vaccine (2704 participants) or placebo (2700 participants). The vaccine regimen consisted of injections of ALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gp120–MF59 adjuvant at months 3, 6, 12, and 18. The primary efficacy outcome was the occurrence of HIV-1 infection from randomization to 24 months. RESULTS : In January 2020, prespecified criteria for non-efficacy were met at an interim analysis; further vaccinations were subsequently halted. The median age of the trial participants was 24 years; 70% of the participants were women. The incidence of adverse events was similar in the vaccine and placebo groups. During the 24-month followup, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P = 0.84). CONCLUSIONS : The ALVAC–gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity.Supported by grants (HHSN272201300033C and HHSN272201600012C) to Novartis Vaccines and Diagnostics (now part of the GlaxoSmithKline [GSK] Biologicals) by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) for the selection and process development of the two gp120 envelope proteins TV1.C and 1086.C; by the Bill and Melinda Gates Foundation Global Health Grant (OPP1017604) and NIAID for the manufacture and release of the gp120 clinical grade material; and by U.S. Public Health Service Grants — UM1 AI068614 to the HIV Vaccine Trials Network (HVTN), UM1 AI068635 to the HVTN Statistical and Data Management Center, and UM1 AI068618 to the HVTN Laboratory Center — from the NIAID. GSK Biologicals contributed financially to the provision of preexposure prophylaxis to trial participants. The South African Medical Research Council supported its affiliated research sites.http://www.nejm.orgam2022School of Health Systems and Public Health (SHSPH

Determination of the refractive index of water-dispersible granules for use in laser diffraction experiments

Modern laser light scattering equipment can cover a very broad particle size range by using complex algorithms, such as the Mie theory. A disadvantage of this theory, however, is that it requires the knowledge of the refractive index of the particles, which is not straightforward for powdered organic substances. In this study, thiram, a common dithiocarbamate fungicide, was used as a model compound. In a first part, a method was elaborated to determine the refractive index, based on refractive index measurements of solutions of the compound of interest in a range of solvents. Two different extrapolation techniques were compared. Both techniques were validated by applying them to the determination of the refractive indices of poly(vinyl acetate) and poly(methyl methacrylate). Secondly, the influence of the refractive index value on the generated particle size distribution in the laser diffraction software was investigated. It was observed that widely different particle size distributions can be generated by the laser diffraction software for a single experimental data-set. Therefore, accurate refractive index information is required to obtain reliable particle size distribution results

Determining the refractive index of organic particles for use in laser light scattering measurements

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Determination of the refractive index of water dispersable granules through differential refractometry and its influence in laser diffraction experiments

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