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

Time frame
30 September 2016 - 31 October 2019
Budget
€ 262,663
Active in

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.

Goals

A cure for HIV
50%
Contributed within this project
< 200,000 new HIV infections globally
50%
Contributed within this project

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