Novel anti-HIV vaccines
The main goal of HIV vaccine development is to induce broadly neutralising antibodies (bNAbs) that work against different viral strains. Although some bNAbs have been isolated from infected individuals, none of the vaccines tested so far have managed to elicit such a response in animal models. Clearly, the envelope antigens of the virus represent the most susceptible targets for anti-HIV antibodies. The key objective of the EU-funded 'Next generation HIV-1 immunogens inducing broadly reactive neutralising antibodies' (NGIN) project was to develop a series of viral envelopes that, used as immunogens, would be capable of eliciting bNAbs. Detailed information on the project objectives and results can be found on the project(opens in new window) website. Screening of over 500 individuals revealed the presence of bNAbs in about 25 % of the patients 2–4 years after infection. Interestingly, higher antibody levels were observed in patients infected with the HIV-2 virus. Partners isolated and cloned more than 1800 HIV envelope genes from primary viruses present in individuals who had successfully mounted bNAbs. Of these, seven were chosen to be screened as vaccine candidates in mice and rabbits. Administration of the env protein vaccine alone or preceded by a DNA administration in rabbits was successful in eliciting Nabs. A similar prime-boost regimen administered to macaques induced Nabs in blood but not at mucosal level. Administration of the protein vaccine to mice, in addition to a mucosal chemokine as adjuvant, showed homing of antigen-specific cells to the mucosa. The consortium showed that the inability of HIV-infected individuals to raise specific B lymphocyte-mediated immune responses and generate memory B cells does recover only if antiretroviral treatment is provided early after infection. In in vitro experiments the administration of soluble CD27 antigen improved the differentiation of memory cells to antibody-producing B cells. NGIN's product pipeline generated a set of new envelope-based vaccine antigens that proved to be immunogenic in rabbits and non-human primates. Although their protective effect against infection remains to be determined, they constitute a hopeful step forward in the battle against HIV.
