Accelerating the development of a group A Streptococcus vaccine: an urgent public health need

Group A Streptococcus (GAS) infections cause substantial worldwide morbidity and mortality, mostly associated with suppurative complications such as pharyngitis, impetigo, and non-suppurative immune syndromes such as acute rheumatic fever, rheumatic heart disease, and acute post-streptococcal glomerulonephritis. Deaths occur mostly in children, adolescents, and young adults in particular pregnant women in low- and middle-income countries. GAS strains are highly variable, and a GAS vaccine would need to overcome the issue of multiple strains. Several approaches have been used multivalent vaccines using N-terminal polypeptides of different M protein; conserved M protein vaccines with antigens from the conserved C-repeat portion of the M protein; incorporation selected T- and B-cell epitopes from the C-repeat region in a synthetic polypeptide or shorter single minimal B-cell epitopes from this same region; and non-M protein approaches utilizing highly conserved motives of streptococcal C5a peptidase, GAS carbohydrate and streptococcal fibronectin-binding proteins. A GAS vaccine represents urgent need for this neglected disease and should therefore deserve the greatest attention of international organizations, donors, and vaccine manufacturers.

HIV-vaccines: lessons learned and the way forward

A safe and efficacious preventive HIV vaccine, as part of a comprehensive prevention program, remains among the highest public health priorities. It would be the best tool that could reduce the spread of HIV significantly in the long run. Current AIDS vaccine candidates are unable to induce neutralizing antibodies against primary HIV isolates or only to a very limited and narrow extent, representing a major obstacle in the development of an efficacious HIV vaccine. Clinical efforts have mainly focused on T-cell vaccines such as DNA and various recombinant vectors alone or in prime-boost regimens. The Merck Ad5vaccine not only failed to show efficacy but also was associated with increased risk of HIV acquisition in vaccinees in a Phase IIb trial. While gp120 alone was not efficacious, the ALVAC prime and gp120 boost regimen showed 31% efficacy in a Phase III trial in Thailand. These contrasting results illustrate the limitations of available laboratory assays to assess the vaccine-induced immune responses and the lack of understanding of immune correlates of protection. Efforts should therefore focus on developing vaccine candidates inducing broadly neutralizing antibodies. Similarly, new vector strategies such as replicating vectors should be explored to induce strong and broad T-cell responses in the systemic and mucosal compartments. Innovation in immune assay development and testing algorithms is critically needed. The standardization of more relevant and predictive non-human primate models for immunogenicity and efficacy studies will contribute to better and faster vaccine assessment. HIV vaccine development requires innovative ideas and a sustained long-term commitment of the scientific community, civil society, politicians, and donors and participants for clinical research.Keywords: Clinical trial, efficacy, HIV, Thailand, vaccine

Expanding Capacity and Accelerating AIDS Vaccine Development in Asia / 国際保健医療

 It has been estimated that by 2010, there might be more people living with HIV in Asia than in Africa. There is an urgent need for a safe, effective, accessible and affordable AIDS vaccine suitable for use in Asia. Factors that may hinder the development of AIDS vaccines in Asia include: 1) difficulty in recruiting adequate number of trial participants due to the low incidence of HIV infection in the general population and in defined population groups at high risk for HIV; 2) circulation of multiple HIV genetic subtypes and recombinant forms, and 3) unique geographical diversity of populations, cultures, social and political backgrounds. A proposed strategy to accelerate the development of an effective AIDS vaccine for Asia could be the constitution of a collaborative regional network in support of AIDS vaccine research and development. Collaborations would include 1) promoting the conduct of additional epidemiological studies and establishment of regional vaccine trial cohorts to reach adequate sample size for efficacy trials, 2) developinga regional platform for the conduct of clinical trials at multiple sites and harmonization of legal, regulatory and ethical frameworks to facilitate the review and approval processes, 3) strengthening the regional clinical research capacities and human resources for efficient development and testing of various vaccine candidates; and 4) promoting the development of regional capacities and infrastructures for vaccine production for the conduct of all phases of clinical trials, licensing and future public health use. A collaborative regional network in support of AIDS vaccine research and development will also require strong political commitment and leadership by all regional and international partners playing a significant role in the region.