Progress toward HIV-1 subtype C vaccines: understanding antiviral immune mechanisms and viral adaptation

INTRODUCTION: HIV-1 subtype C (HIV-1C) accounts for most infections globally, with sub-Saharan Africa bearing a disproportionate burden. Despite decades of research and multiple clinical trials, no effective prophylactic vaccine exists for this or any other HIV subtype - and candidate vaccines for subtype C are less well researched than for subtypes occurring most frequently in the developed world. The anticipated reduction in US funding for HIV treatment and prevention programs from 2026 in the regions where subtype C predominates makes the urgency of developing an effective vaccine or vaccines more acute than ever. AREAS COVERED: This review explores the experimental vaccine investigations and clinical trials that have dealt specifically with vaccines for HIV-1 subtype C viruses, including coverage of the vectors and protein antigens used in pre- and clinical trials, vaccine regimes tested in animals and in humans, and modifications made to antigens to stabilize them and enhance immunogenicity, in the light of findings for other subtypes. EXPERT OPINION: The appropriateness and feasibility of various vaccine approaches are discussed, and suggestions are made with regard to strategies for coping with the prevention of HIV infection in developing countries with high subtype C prevalence.