First Phase I human clinical trial of a killed whole HIV 1 vaccine: demonstration of its safety and enhancement of anti HIV antibody responses
Background Vaccination with inactivated (killed) whole virus particles has been used to prevent a wide range of viral diseases. However, for an HIV vaccine this approach has been largely negated due to inherent safety concerns, despite the ability of killed whole virus vaccines to generate a strong, predominantly antibody mediated immune response in vivo. HIV 1 Clade B NL4 3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence for the Env signal peptide with that of honeybee melittin signal peptide to produce a less virulent and more replication efficient virus. This genetically modified virus (gmHIV 1NL4 3) was inactivated and formulated as a killed whole HIV vaccine, and then used for a Phase I human clinical trial (Trial Registration: Clinical Trials NCT01546818) The gmHIV 1NL4 3 was propagated in the A3.01 human T cell line followed by virus purification and inactivation with aldrithiol 2 and g irradiation. Thirty three HIV 1 positive volunteers receiving cART were recruited for this observer blinded, placebo controlled Phase I human clinical trial to assess the safety and immunogenicity.Results Genetically modified and killed whole HIV 1 vaccine, SAV001, was well tolerated with no serious adverse events. HIV 1NL4 3 specific PCR showed neither evidence of vaccine virus replication in the vaccine virus infected human T lymphocytes in vitro nor in the participating volunteers receiving SAV001 vaccine. Furthermore, SAV001 with adjuvant significantly increased the pre existing antibody response to HIV 1 proteins. Antibodies in the plasma of vaccinees were also found to recognize HIV 1 envelope protein on the surface of infected cells as well as showing an enhancement of broadly neutralizing antibodies inhibiting tier I and II of HIV 1 B, D, and A subtypes.ConclusionThe killed whole HIV vaccine, SAV001, is safe and triggers anti HIV immune responses. It remains to be determined through an appropriate trial whether this immune response prevents HIV infection.
Retrovirology