Britta Wahren Group
photo: Lennart Nilsson, SMI photo archive
Kunskapskanalen Interview 3 May 2010
An Effective HIV Vaccine
Genetic vaccines have generated wide-spread interest for many applications, since DNA encoding a microbial gene results in in vivo expression of the desired gene, protein production and presentation as an endogenous foreign antigen. Due to these properties the polymorphic H LA system of humans can be targeted even with highly variable virus proteins, such as Human immunodeficiency virus (HIV), hepatitis C virus (HCV) or influenza.
HIV genes were constructed covering the highly variable sites of HIV envelopes. For structural genes the gag subtypes A and B were created, for the less variable parts the reverse transcriptase and regulatory gene rev. Immunodominant non-neutralizing sequences were mutated, certain genes were changed to reduce toxicity and partial codon optimization was made to increase expression. Small size plasmids as well as divided doses of dominant versus subdominant genes together with a potent adjuvant for DNA showed potent and broad crossreactivity in preclinical studies. A boost with recombinant MVA including subtypes A and E genes effectively boosted humoral, helper cell, and cytotoxic responses. This vaccine prime boost schedule has resulted in a very high immunogenicity in a clinical phase 1 prophylactic study.
The present aims with this very effective HIV vaccine are one prophylactic vaccine study in Tanzania and two phase II studies in Africa. Research questions include HIV viral variation and induction of immunity to resistance, and innate (NK) responses during disease and after vaccination. We will also study the duration of memory after genetic immunization, recombinant virus or protein boosting, amplification of immune responses preclinically and in humans with novel adjuvants.