Accelerating the development of a safe and effective HIV vaccine: HIV vaccine case study for the Decade of Vaccines

doi:10.1016/j.vaccine.2012.10.115

Vaccine

Volume 31, Supplement 2, 18 April 2013, Pages B204-B208

https://doi.org/10.1016/j.vaccine.2012.10.115 Get rights and content

Abstract

Human immunodeficiency virus (HIV), the etiologic agent that causes AIDS, is the fourth largest killer in the world today. Despite the remarkable achievements in development of anti-retroviral therapies against HIV, and the recent advances in new prevention technologies, the rate of new HIV infections continue to outpace efforts on HIV prevention and control. Thus, the development of a safe and effective vaccine for prevention and control of AIDS remains a global public health priority and the greatest opportunity to eventually end the AIDS pandemic. Currently, there is a renaissance in HIV vaccine development, due in large part to the first demonstration of vaccine induced protection, albeit modest, in human efficacy trials, a generation of improved vaccine candidates advancing in the clinical pipeline, and newly defined targets on HIV for broadly neutralizing antibodies. The main barriers to HIV vaccine development include the global variability of HIV, lack of a validated animal model, lack of correlates of protective immunity, lack of natural protective immune responses against HIV, and the reservoir of infected cells conferred by integration of HIV's genome into the host. Some of these barriers are not unique to HIV, but generic to other variable viral pathogens such as hepatitis C and pandemic influenza. Recommendations to overcome these barriers are presented in this document, including but not limited to expansion of efforts to design immunogens capable of eliciting broadly neutralizing antibodies against HIV, expansion of clinical research capabilities to assess multiple immunogens concurrently with comprehensive immune monitoring, increased support for translational vaccine research, and engaging industry as full partners in vaccine discovery and development.

Highlights

► HIV, the etiologic agent that causes AIDS, is the fourth largest killer in the world today. ► The rate of new HIV infections continues to outpace efforts on HIV prevention and control. ► The development of a safe and effective vaccine for prevention and control of AIDS remains a global public health priority.

Section snippets

Background

Nearly thirty years since the identification of human immunodeficiency virus (HIV) as the etiologic agent that causes AIDS [1], [2], more than 60 million persons have become HIV infected, with over 25 million succumbing to AIDS, over 33 million living with HIV, and over 7000 new infections daily [3]. HIV is the fourth largest killer in the world today with an annual toll of approximately 2 million deaths, and the virus continues to cause significant morbidity and mortality, particularly in

Current situation

Though multiple HIV vaccine approaches have been developed over the last three decades, including peptides, proteins, nucleic acid, viral vectors and prime–boost combination regimens, only three HIV vaccine approaches have completed human efficacy trials. The first was a recombinant protein (HIV gp120) adjuvanted in alum, and this candidate failed to prevent or control HIV infection in men who have sex with men and in injection drug users [4]. The second, a recombinant adenovirus type 5

Main barriers and challenges

HIV presents formidable obstacles for successful vaccine development. These challenges include:

1.
The unprecedented global variability of HIV. The virus exhibits a remarkable degree of genetic variability in the host, driven by host immune pressure and accelerated by the error-prone nature of its reverse-transcriptase, together with high rates of virus production and high frequency of recombination. Thus, a safe and effective HIV vaccine has to protect against a plethora of globally diverse

Goals and vision for the next decade of HIV vaccine development

With an HIV vaccine the best hope for eventually ending the AIDS pandemic, the vision guiding the multiple stakeholders comprising the Global HIV Vaccine Enterprise is “A World Without AIDS”. HIV vaccine development will be an iterative process. On the path toward achieving this vision, the primary goal for HIV vaccine development for the next decade is to design and advance, to efficacy trials, vaccine candidate(s) with product profiles capable of eliciting protective immune responses for

Proposed strategy and actions

To achieve these ambitious goals the following strategy and actions are proposed:

Strategy	Proposed actions
1. Ensure essential funding is available to achieve HIV vaccine development objectives for the next ten years.	• Major stakeholders should develop a ten year R&D plan for HIV vaccine development, and a concrete funding proposal including proposed mechanism(s) for funding the plan. • Broaden the diversity of funder's worldwide supporting HIV vaccine development.

2. Ensure clinical trial capacity

Summary and conclusions

In order to successfully implement the proposed strategies and actions, a multi-year (we proposed ten-year-Strategy 1) HIV vaccine development plan needs to be developed, debated by major stakeholders, and implemented. We envision a small-working group including academic, industry, government, and NGO representatives would need to draft the plan, including estimates of the costs for implementation of the initiatives defined in the plan. Long-term committed funding is key to accelerating vaccine

Conflict of interest

All authors declare that they have no conflicts of interest.

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ReviewAccelerating the development of a safe and effective HIV vaccine: HIV vaccine case study for the Decade of Vaccines

Abstract

Highlights

Section snippets

Background

Current situation

Main barriers and challenges

Goals and vision for the next decade of HIV vaccine development

Proposed strategy and actions

Summary and conclusions

Conflict of interest

Lancet

Vaccine

Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS)

Science

Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS

Science

Global report: UNAIDS report on the global AIDS epidemic 2010

Review
Accelerating the development of a safe and effective HIV vaccine: HIV vaccine case study for the Decade of Vaccines