Sex-associated differences in immune responses to a novel HIV-1 envelope trimer vaccine

It is widely recognised that current human immunodefiency virus (HIV) prevention tools alone are insufficient to bring about a sustainable end to the HIV and acquired immunodefiency syndrome (AIDS) epidemic as a public health threat. In addition to achieving higher coverage of existing prevention tools, we need to develop a safe and at least moderately effective vaccine. Developing an HIV-vaccine is largely complicated by the immense variability of the virus. The most likely to succeed solution to this dilemma is the induction of broadly neutralising antibodies (bNAbs), capable of protecting against a wide variety of HIV strains. The work in this thesis describes preclinical and clinical studies investigating the safety and immunological properties of the ConM SOSIP.v7 gp140 vaccine, a first generation native-like HIV Env trimer vaccine, based on an artificial consensus sequence of all isolates in the most widespread HIV-1 Major group (M), responsible for over 90% of HIV infections worldwide. The vaccine was found to be safe and capable of eliciting cross-reactive binding antibody responses in non-human primates and humans, making it an interesting boosting immunogen candidate in a sequential immunisation strategy focused on bNAb induction. Various chapters reveal sex-associated differences in key immunological outcomes such as antibody binding and neutralisation, highlighting the need to take sex-based differences into consideration when assessing HIV-1 vaccine candidates and adjuvants, from the earliest developmental stages up to extensive vaccine efficacy studies.