A randomized, controlled trial of an aerosolized vaccine against measles.

BACKGROUND: Aerosolized vaccine can be used as a needle-free method of immunization against measles, a disease that remains a major cause of illness and death. Data on the immunogenicity of aerosolized vaccine against measles in children are inconsistent. METHODS: We conducted an open-label noninferiority trial involving children 9.0 to 11.9 months of age in India who were eligible to receive a first dose of measles vaccine. Children were randomly assigned to receive a single dose of vaccine by means of either aerosol inhalation or a subcutaneous injection. The primary end points were seropositivity for antibodies against measles and adverse events 91 days after vaccination. The noninferiority margin was 5 percentage points. RESULTS: A total of 1001 children were assigned to receive aerosolized vaccine, and 1003 children were assigned to receive subcutaneous vaccine; 1956 of all the children (97.6%) were followed to day 91, but outcome data were missing for 331 children because of thawed specimens. In the per-protocol population, data on 1560 of 2004 children (77.8%) could be evaluated. At day 91, a total of 662 of 775 children (85.4%; 95% confidence interval [CI], 82.5 to 88.0) in the aerosol group, as compared with 743 of 785 children (94.6%; 95% CI, 92.7 to 96.1) in the subcutaneous group, were seropositive, a difference of -9.2 percentage points (95% CI, -12.2 to -6.3). Findings were similar in the full-analysis set (673 of 788 children in the aerosol group [85.4%] and 754 of 796 children in the subcutaneous group [94.7%] were seropositive at day 91, a difference of -9.3 percentage points [95% CI, -12.3 to -6.4]) and after multiple imputation of missing results. No serious adverse events were attributable to measles vaccination. Adverse-event profiles were similar in the two groups. CONCLUSIONS: Aerosolized vaccine against measles was immunogenic, but, at the prespecified margin, the aerosolized vaccine was inferior to the subcutaneous vaccine with respect to the rate of seropositivity. (Funded by the Bill and Melinda Gates Foundation; Measles Aerosol Vaccine Project Clinical Trials Registry-India number, CTRI/2009/091/000673.).

The blueprint for vaccine research & development: walking the path for better TB vaccines.

Much progress has been made in TB vaccine research over the past ten years, and a series of new live genetically altered mycobacterial vaccines, viral-vectored vaccines and sub-unit vaccines composed of recombinant antigens are presently in clinical development phases. A series of challenges remain, however, to be addressed in order to develop new and better candidate TB vaccines, especially an expansion of our knowledge of what constitutes protective immunity in TB, the identification of the most suitable vaccination strategies, the capacity and infrastructure to conduct large-scale trials in endemic countries, the investment in vaccine manufacturing capacity, and the development of effective regulatory pathways that shorten review timelines. In this brief paper, we review how the Vaccine Blueprint places itself in the continuation and expansion of two groundbreaking initiatives taking place over the last two years, that is, an invigorated Global Plan to Stop TB 2011-2015 that gives a clear emphasis on Research and Development, and the International Roadmap for TB Research, that identifies key priorities for research on TB vaccines, spanning from the most fundamental research aspects to the more field-based epidemiological aspects.

A global pandemic influenza vaccine action plan.

In case of an influenza pandemic, the world will be in a situation where potential vaccine supply will fall short by several billion doses from global needs. The World Health Organization (WHO) convened in Geneva on May 2-3, 2006 a consultation of all stakeholders in influenza vaccines and immunization to identify practical solutions to fill this gap. The consultation resulted in a global action plan outlining promising specific strategies to increase influenza vaccine production and surge-capacity before and during an influenza pandemic. Although the timing and severity of the next influenza pandemic cannot be predicted, vaccines are considered the one of the most important medical interventions for reducing morbidity and mortality if and when such an event occurs. Despite this acknowledged role, current limitations on influenza vaccine manufacturing capacity mean that, should a pandemic virus emerge in the near future, vaccine supplies would fall short of the anticipated global demand by several billion doses. Concern about this situation was formally acknowledged in May 2005, when the World Health Assembly approved a resolution [1] on strengthening pandemic influenza preparedness and response. That resolution called on the World Health Organization (WHO) to seek solutions with international and national partners, including the private sector, to reduce the present global shortage of influenza vaccines. More specifically, the resolution asked WHO to look at strategies for economizing on the use of antigen and transferring production technologies from industrialized to developing countries. In response to this request, WHO convened a consultation from 2-3 May 2006 attended by representatives of the major stakeholders in the area of influenza vaccines and immunization. The consultation had two main objectives: (1) To prepare a global action plan with specific short-, medium-, and long-term activities designed to increase influenza vaccine production and surge-capacity, to identify key obstacles and driving forces, and to estimate funding needs.(2) To strengthen the engagement and collaboration of key partners and stakeholders.