The GREAT project will test an improved prototype HIV vaccine in high-risk and vulnerable African populations.

Progressing a second-generation HIV vaccine

An HIV vaccine is likely to be central to global efforts to eradicate the virus. However, developing an effective HIV vaccine has been highly challenging. One major issue is the extreme diversity of HIV – meaning that protection against one strain may not afford protection against another. In addition, the virus rapidly evolves within individual patients, generating variants that may evade vaccine-induced protection.

The challenge

Over many years, a group led by Professor Tomáš Hanke has been developing an HIV vaccine capable of targeting a wide range of HIV variants. HIV control is likely to depend on different vaccines that elicit either T cell- or antibody-based protection, and his group’s focus has been a vaccine that generates protective T cells. His team has been aiming to identify highly conserved HIV structures that are shared across different HIV variants and are thought to be critical to its ability to multiply and spread. These structural antigens are delivered via commonly used DNA-based vectors.

Recently, Professor Hanke’s team has developed a second-generation vaccine, tHIVconsvX, that builds on this promising platform but adds new features. The new vaccine is a ‘mosaic’: as well as several widely shared antigens, it also includes multiple variants of antigens known to stimulate strong T-cell responses. In addition, it incorporates antigens that, in patients, are associated with relatively good control of HIV replication. This extensive combination of antigens in a single vaccine, partnered with a potent delivery system, has generated encouraging results in animal models and initial human studies.

The GREAT project will test the safety of tHIVconsvX, as well as its ability to generate HIV-specific immune responses. The project team will work with a range of marginalised communities, including fishing communities around Lake Victoria, male and female sex workers, and men who have sex with men.

The project

The GREAT trial will generate evidence that will indicate whether tHIVconsvX is sufficiently potent to justify a phase III efficacy trial. Moreover, the consortium’s capacity building and extensive community engagement will provide a platform for a pivotal phase III study, should one be merited.

Impact


crucial in

widening African

children’s access

to antiretrovirals

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

An HIV vaccine is likely to be central to global efforts to eradicate the virus. However, developing an effective HIV vaccine has been highly challenging. One major issue is the extreme diversity of HIV – meaning that protection against one strain may not afford protection against another. In addition, the virus rapidly evolves within individual patients, generating variants that may evade vaccine-induced protection.

Over many years, a group led by Professor Tomáš Hanke has been developing an HIV vaccine capable of targeting a wide range of HIV variants. HIV control is likely to depend on different vaccines that elicit either T cell- or antibody-based protection, and his group’s focus has been a vaccine that generates protective T cells. His team has been aiming to identify highly conserved HIV structures that are shared across different HIV variants and are thought to be critical to its ability to multiply and spread. These structural antigens are delivered via commonly used DNA-based vectors.

Recently, Professor Hanke’s team has developed a second-generation vaccine, tHIVconsvX, that builds on this promising platform but adds new features. The new vaccine is a ‘mosaic’: as well as several widely shared antigens, it also includes multiple variants of antigens known to stimulate strong T-cell responses. In addition, it incorporates antigens that, in patients, are associated with relatively good control of HIV replication. This extensive combination of antigens in a single vaccine, partnered with a potent delivery system, has generated encouraging results in animal models and initial human studies.

The GREAT project will test the safety of tHIVconsvX, as well as its ability to generate HIV-specific immune responses. The project team will work with a range of marginalised communities, including fishing communities around Lake Victoria, male and female sex workers, and men who have sex with men.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The GREAT trial will generate evidence that will indicate whether tHIVconsvX is sufficiently potent to justify a phase III efficacy trial. Moreover, the consortium’s capacity building and extensive community engagement will provide a platform for a pivotal phase III study, should one be merited.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact

Projects: CAPRISA 018 study

Project lead: Professor Salim Abdool Karim, Centre for the AIDS Programme of Research in South Africa, South Africa

Countries involvedFrance, The Netherlands, South Africa

Target population(s): Women

Year funded: 2017

EDCTP funding: €9.8 M

Total project funding: €11.4M plus donation of study drugs

About us

The European & Developing Countries Clinical Trials Partnership (EDCTP) is a public–public partnership between 14 European and 16 African countries, supported by the European Union. EDCTP’s vision is to reduce the individual, social and economic burden of poverty-related infectious diseases by affecting sub-Saharan Africa. EDCTP’s mission is to accelerate the development of new or improved medicinal products for the identification, treatment and prevention of infectious diseases, including emerging and re-emerging diseases, through pre- and postregistration clinical studies, with emphasis on phase II and III clinical trials. Our approach integrates conduct of research with development of African clinical research capacity and networking. The second EDCTP programme is implemented by the EDCTP Association supported under Horizon 2020, the European Union’s Framework Programme for Research and Innovation.

Contact us

For more information, please contact us or leave a message using this form.
Please enter your name
Please enter a correct e-mail address
Please enter a comment
Thank you! Your message has been sent.
Something went wrong while submitting the form. Try again.

Share this publication

Forward this page by e-mail or share it directly on social media.

Search

Enter a search term to search the EDCTP publications.
Minimal length to search is 3 characters

This publication uses cookies

We use functional and analytical cookies to improve our website. In addition, third parties place tracking cookies to display personalised advertisements on social media. By clicking accept you consent to the placement of these cookies.