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European centralized facility for preclinical hiv-1 vaccine development

Objective

The broad aims of this project are to provide European Researchers with a critical centralised research resource for the development and evaluation of Vaccine Biotechnology initiatives. It is the aim to accelerate the preclinical development and evaluation of European vaccine candidates as effective products to the clinic. This facility and its expert staff will utilise unique resources and lend their expertise to widely provide a large number of European Researchers with valuable assistance to facilitate strategic development and to improve vaccine efficacy. To assist in the research development of new vaccine strategies and technologies, different nonhuman primate (NHP) models as well as the immunological assays and expertise used to evaluate protective immune responses will be provided in a standardised setting for fair and unbiased comparison.

The specific objectives of this programme are to;
I. Widely provide the primate research expertise and resources for the stepwise development and evaluation of safe, effective vaccines for the prevention of infection and development of AIDS
a) Evaluation and facilitated development of proposed vaccine candidates
b) Determination of components important for protective (especially mucosal) immunity
II. Identify markers / parameters of protective immunity from HIV infection and AIDS along with clinical correlates from interactive EC Concerted Actions.
III. Evaluate mucosal vaccine delivery/strategies and study processes to induce protective mucosal immune responses.
To study immunological mechanisms of mucosal protection from HIV.
IV. To further develop suitable primate models for vaccine development.

These objectives will be achieved through the use of nonhuman primate models for HIV-1 infection and AIDS. This programme will be co-ordinated closely with EUPREN and PVEN activities for efficient, ethical and research standards set for the use of primates in EU countries. A number of HIV-1 vaccine trials performed at this centre in the past have clearly highlighted the value of the chimpanzee model. One successful candidate HIV-1 vaccine tested at this centre has now moved to clinical trials. Another HIV vaccine candidate could only be tested in chimpanzees because of its limited host range, proved not to be a suitable vaccine, saving years of lost investment in expensive clinical trials. However, the demand for HIV-1 vaccine testing in chimpanzees is too great as are the ethical considerations and economics of their life-long care. Hence, this new proposal emphasises and provides the science for stepwise evaluation and development of HIV-1 vaccine candidates to be selected for true efficacy testing in chimpanzees. The nature of the immune responses induced by different vaccine protocols will be analysed and compared to other vaccine candidates tested in primate models as well as clinical trials. Efficacy of these vaccine strategies will be determined by stepwise evaluation in NHP models. The models utilised include the SHIV rhesus model, the SIV rhesus model of AIDS, and the HIV-1 chimpanzee model of HIV-1 infection in man. By determining the nature of the immune responses, and correlating them with protection from challenge in NHP's, important markers of protective immunity will be identified. Based on the information provided by this Centralised Facility, collaborating centres can modify and improve their vaccines and approaches. A selection of competitive and innovative vaccine approaches by European Researchers has already begun. Over the last few years proposals received in response to annual advertisements placed in 'Nature' have been externally peer reviewed and advice to support the most promising proposals has been given. Many of these are being tested in NHP in the current programme. Annual calls for new proposals will continue if the programme is renewed. The process of re-evaluation and development will continue. Vaccine candidates which pass immunological, safety and efficacy criteria will be developed and eventually tested in chimpanzees for protection against intravenous and mucosal challenge, setting the stage for clinical trials.

PROPOSAL SUMMARY: The broad aims of this proposal are to provide European Researchers with a critical centralised research resource for the development and evaluation of Vaccine Biotechnology initiatives. It is the aim to accelerate the preclinical development and evaluation of European vaccine candidates as effective products to the clinic. This facility and its expert staff will utilize unique resources and lend their expertise to widely provide a large number of European Researchers with valuable assistance to facilitate strategic development and to improve vaccine efficacy. To assist in the research development of new vaccine strategies and technologies, different nonhuman primate (NHP) models as well as the immunological assays and expertise used to evaluate protective immune responses will be provided in a standardized setting for fair and unbiased comparison. This Centralized Facility proposal was ranked as #1 by consensus out of 117 proposals on AIDS research in the first call of Biomed 2. As a result of the first round, after consultation with the Commission, it was decided to fund the first year (phase 1) of the work plan. The proposers were advised to resubmit the proposal for the current call for complementary funding, meanwhile allowing for update and the inclusion of new developments in the workplan for further trials.

The specific objectives of this programme are to;
I. Widely provide the primate research expertise and resources for the step is development and evaluation of safe, effective vaccines for the prevention o infection and development of AIDS: a) Evaluation and facilitated development of proposed vaccine candidates; b) Determination of components important for protective (including mucosal) immunity;
II. Identify markers / parameters of protective immunity from HIV infection and AIDS along with clinical correlates from interactive EC Concerted Actions;
III.Evaluate mucosal vaccine delivery/strategies and study processes to induce protective mucosal immune responses. To study immunological mechanisms of mucosal protection from HIV;
IV. To further develop suitable primate models for vaccine development.

These objectives will be achieved through the use of nonhuman primate models for HIV-1 infection and AIDS. This programme will be coordinated closely with EUPREN and PVEN activities for efficient ethical and research standards set for the use of primates in EU countries. A number of HIV-1 vaccine trials performed at this centre in the past have clearly highlighted the value of the chimpanzee model. One successful candidate HIV-1 vaccine tested at this centre has now moved to clinical trials. Another HIV vaccine candidate could only be tested in chimpanzees because of its limited host range, proved not to be a suitable vaccine, saving years of lost investment in expensive clinical trials. However, the demand for HIV-1 vaccine testing in chimpanzees is too great as are the ethical considerations and economics of their life-long care. Hence, this new proposal emphasises and provides the science for stepwise evaluation and development of HIV-1 vaccine candidates to be selected for true efficacy testing in chimpanzees.

The nature of the immune responses induced by different vaccine protocols will be analysed and compared to other vaccine candidates tested in primate models as well as clinical trials. Efficacy of these vaccine strategies will be determined by stepwise evaluation in NHP models. The model utilised include the SHIV rhesus model of HIV-1, the SIV rhesus model of AIDS, and the HIV-1 chimpanzee model of HIV-1 infection in man. By determining the nature of the immune responses, and correlating them with protection from challenge in NHP's, important markers of protective immunity will be identified. Based on the information provided by this Centralized Facility, collaborating centres can modify and improve their vaccines and approaches. A selection of competitive and innovative vaccine approaches by European Researchers has already begun. Over the last few years proposals received in response to annual advertisements placed in "Nature" have been externally peer reviewed and advice to support the most promising proposals has been given. Many of these are being tested in NHP in the current programme. Annual calls for new proposals will continue if the programme is renewed. The process of re-evaluation and development will continue.

Vaccine candidates which pass immunological, safety and efficacy criteria will be developed and eventually tested in chimpanzees for protection against intravenous and mucosal challenge, setting the stage for clinical trials.

Keywords: HIV-1 vaccine development, efficacy, preclinical, mucosal, protective immunity, non-human primate models, chimpanzees.

Funding Scheme

CON - Coordination of research actions

Coordinator

FOUNDATION BIOMEDICAL PRIMATE RESEARCH CENTRE
Address
157,Lange Kleiweg 139
2288 GJ Rijswijk Zh
Netherlands