HIV envelope trimer vaccines that engage desirable germline antibodies
HIV envelope trimer vaccines that engage desirable germline antibodies
Project
Despite 30 years of intensive research, an effective HIV-1 vaccine remains elusive. One of the major challenges is the induction of broadly neutralizing antibodies (bNAbs) by envelope glycoprotein (Env) based vaccines. Since 2009 a wealth of new bNAbs have been identified that can be used as templates for vaccine design. However, there is accumulating evidence that HIV-1 Env vaccines generally are not able to bind to the unmutated germline ancestors of these bNAbs, which may be the reason that these vaccines are not able to induce similar types of bNAbs. Here we propose to generate Env trimer vaccines specifically designed to bind to the unmutated germline ancestors of known human bNAbs. We have 3 approaches to achieve this goal. 1. A patient-based approach: by screening early Env sequences from patients from the Amsterdan Cohort that developed bNAbs. 2. A structure-based approach: by computationally designing Env surfaces that are able to bind unmutated germline ancestors of bNAbs. 3. A library screening approach: by screening randomly generated variant Env trimers, displayed on the surface of mammalian cells, by FACS. Collectively, these approaches should allow us to generate Env vaccines that are more efficient in generating bNAbs.
Project details
Amsterdam
Objectives
Here we propose to generate Env trimer vaccines specifically designed to bind to the unmutated germline ancestors of known human bNAbs. We have 3 approaches to achieve this goal. 1. A patient-based approach: by screening early Env sequences from patients from the Amsterdan Cohort that developed bNAbs. 2. A structure-based approach: by computationally designing Env surfaces that are able to bind unmutated germline ancestors of bNAbs. 3. A library screening approach: by screening randomly generated variant Env trimers, displayed on the surface of mammalian cells, by FACS. Collectively, these approaches should allow us to generate Env vaccines that are more efficient in generating bNAbs.
Community groups
scientific community
People at risk for HIV
Background
Despite 30 years of intensive research, an effective HIV-1 vaccine remains elusive. One of the major challenges is the induction of broadly neutralizing antibodies (bNAbs) by envelope glycoprotein (Env) based vaccines
One of the major challenges is the induction of broadly neutralizing antibodies (bNAbs) by envelope glycoprotein (Env) based vaccines. Since 2009 a wealth of new bNAbs have been identified that can be used as templates for vaccine design. However, there is accumulating evidence that HIV-1 Env vaccines generally are not able to bind to the unmutated germline ancestors of these bNAbs, which may be the reason that these vaccines are not able to induce similar types of bNAbs.