Scientific Publications

A DNA MVA based candidate human immunodeficiency virus vaccine for Kenya induces multi specific T cell responses in rhesus macaques

Wee EG, Patel S, McMichael AJ, Hanke T

A DNA/MVA-based candidate human immunodeficiency virus vaccine for Kenya induces multi-specific T cell responses in rhesus macaques. J. Gen. Virol. 2002;83(Pt 1):75-80

doi: 10.1099/0022-1317-83-1-75

Abstract

The minimum requirement for candidate human immunodeficiency virus (HIV) vaccines to enter clinical evaluation in humans should be their demonstrable immunogenicity in non-human primates: induction of antibodies neutralizing primary HIV isolates or elicitation of broad T cell-mediated immune responses. Here, we showed in rhesus macaques that the very same vaccines that had entered clinical trials in Oxford and Nairobi, plasmid pTHr.HIVA DNA and recombinant modified vaccinia virus Ankara MVA.HIVA in a prime-boost protocol (Hanke & McMichael, Nature Medicine 6, 951-955, 2000), induced cellular immune responses specific for multiple HIV-derived epitopes. This was demonstrated by using the intracellular cytokine staining and ELISPOT assays detecting interferon-gamma and pools of peptides employed in the clinical studies. These results have both boosted our expectations for the performance of these vaccines in humans and increased our confidence about the choice of these assays as the primary readouts in the on-going human trials.

Scientific Publications

Design and tests of an HIV vaccine

McMichael A, Mwau M, Hanke T

Design and tests of an HIV vaccine. Br. Med. Bull. 2002;62:87-98

doi: 10.1093/bmb/62.1.87

Abstract

It is likely that a successful vaccine against HIV will need to stimulate the innate immune system, generate high levels of neutralising antibody, strong cellular immune responses, and mucosal immunity. Early efforts to develop HIV vaccines attempted to use the virus glycoprotein, gp120, to induce neutralising antibody, but did not take into account the trimeric structure of the native glycoprotein or the complex nature of the CD4 and chemokine receptor binding sites. Recently, attention has been focused on cellular immune responses, particularly T-cell cytotoxicity, based on evidence from the SIV model and from exposed and uninfected humans. Recent experiments in macaques and man suggest that a prime boost regimen using DNA and recombinant pox virus is highly effective at stimulating cellular immunity. However, in addition to the problems of generating neutralising antibodies and mucosal immunity, the difficulty of inducing broad cellular responses able to protect against all clades of HIV, remains an important issue.

Scientific Publications

Initial lessons from public private partnerships in drug and vaccine development

Wheeler C, Berkley S

Initial lessons from public-private partnerships in drug and vaccine development. Bull. World Health Organ. 2001;79(8):728-34

Abstract

In recent years, venture capital approaches have delivered impressive results in identifying and funding promising health discoveries and bringing them to market. This success has inspired public sector experiments with 'social venture capital' approaches to address the dearth of affordable treatment and prevention for diseases of the developing world. Employing the same focus on well-defined and measurable objectives, and the same type of connections to pool and deploy resources as their for-profit counterparts, social venture capitalists seek to use the tools and incentives of capitalism to solve one of its biggest failures: the lack of drugs and vaccines for diseases endemic to low-income populations. As part of a larger trend of partnerships emerging in health product donation and distribution, public-private partnerships for pharmaceutical development have led research and development (R&D) efforts to generate more accessible and efficacious products for diseases such as malaria, tuberculosis, and AIDS. In this article, three R&D-focused partnerships are explored: the International AIDS Vaccine Initiative; the Medicines for Malaria Venture; and the newly formed Global Alliance for TB Drug Development. The article highlights key elements essential to the success of these ventures.

Scientific Publications