SCRIPPS CONSORTIUM FOR HIV/AIDS VACCINE DEVELOPMENT (CHAVD)

Innovating towards an HIV vaccine

Our overall mission is to define immunogens and immunization regimens that can guide product development strategies for a preventive human AIDS vaccine.

HIV — A TRICKY VIRUS

Making an HIV vaccine is a difficult and complex task that has eluded scientists for more than 35 years.

Conventional vaccines such as live attenuated and killed virus fail against the highly variable and evasive HIV. Our approach is based on the induction of broadly neutralizing antibodies (bnAbs) to the envelope trimer on the surface of the virus.

37.9 mil

people living with HIV/AIDS worldwide

1.7 mil

new infections per year

4

new infections every minute

CREATING AN EFFECTIVE VACCINE

To design a successful HIV vaccine that elicits protective antibodies and induces long-term protective immunity, we propose integrated efforts focused on three areas.

01.

B Cell and Antibody Research

Concentrates on developing immunogens and immunization strategies that induce broadly protective antibody responses to HIV. Focus on broadly neutralizing antibodies is strong as they have proven to be protective in robust non-human primate models and because some non-neutralizing antibodies may have protective qualities that might be exploited in vaccine discovery.

02.

Approaches to Vaccine Design

GERMLINE-TARGETING: Priming immunogen engineered to broadly activate precursors within a bnAb class; boost immunogens are successively more native-like.

IMMUNOFOCUSING: Immunogen sequence designed to focus responses to one or more particular epitopes.

LINEAGE-BASED DESIGN: Immunogens derived from sequence of Env variants in case studies of bnAb development from natural infection.

03.

Clinical Trials and Evaluation

For consideration as a clinical candidate, an immunogen will first be expected to meet a number of criteria. We will only pursue development and clinical testing of vaccines that elicit bnAbs under physiological conditions relevant to humans. Detailed analysis and understanding of immune responses in humans will be crucial to iterative vaccine design improvements. Frequencies of polyclonal off-target B cells compete for immunodominance not only during priming but at all stages of sequential vaccination. Polishing trimer immunogens should generally be validated as part of a bnAb-inducing regimen, but if proposed alone must induce nAbs in NHPs.

"We seek to discover immunogens and immunization strategies that induce antibody and cellular immune responses that are able to protect against exposure to the enormous diversity of global HIV isolates."

CHAVD Mindset

Fig 1.