An Introductory Factsheet
This fact sheet provides basic information on preventive AIDS vaccines. For more basic fact sheets in this series on emerging HIV prevention strategies visit www.avac.org/intro.
What Is an AIDS Vaccine?
A preventive vaccine is a substance that teaches the immune system how to create protective immune responses against a particular pathogen. Scientists have been looking for an AIDS vaccine to prevent infection in HIV-negative people for over 30 years. They have achieved significant discoveries about HIV, the immune system and vaccinology in general. But no HIV/AIDS vaccine exists today.
Scientists are also developing therapeutic vaccines that could build immune strength in HIV-positive people to reduce their risk of getting sick, and ideally, their reliance on antiretroviral treatment. Therapeutic vaccines are also being evaluated as part of cure strategies (see www.avac.org/cure). This factsheet concentrates on preventive vaccines being developed for use by HIV-negative people.
What Are Some of the Key Developments in the AIDS Vaccine Field?
AIDS vaccine development has proven extremely challenging. HIV comes in many varieties and mutates rapidly, and it primarily attacks the very cells needed to mount an effective immune response. In fact, most vaccines to date have been developed by replicating the immune response of a person who had successfully eliminated an invading pathogen. Since no human to date has eliminated HIV using their own immune system, scientists cannot employ that important strategy.
Proof of Concept That an AIDS Vaccine Can Reduce Risk of Infection
Five AIDS vaccine efficacy trials failed to show any impact on preventing infection. But in 2009 a trial called RV144 released results showing that those who received the vaccine were 31 percent less likely to become infected than those who received placebo. The RV144 vaccine regimen was a combination "prime-boost" vaccine requiring six injections over a six-month period. It used a vector derived from canary pox, called ALVAC, to "prime" the immune system. The "boost" was a manufactured protein modeled after the gp120 protein on the outer surface of the virus. RV144 results were the first proof of concept that a preventive AIDS vaccine was possible, and a major milestone for the field. RV144 was conducted at sites in Thailand only, and 31 percent is a relatively modest level of efficacy. A primary focus for the field has been to build on RV144 results toward a vaccine for licensure.
The P5 Initiative
An international consortium known as the Pox-Protein Public Private Partnership (or P5) is working together to examine whether changing the RV144 vaccine regimen, e.g., replacing the protein with a better formulation of gp120; adding an "adjuvant", a substance to increase the body's response to the vaccine; and/or increasing the number of boosts could result in greater efficacy.
The HIV Vaccine Trials Network (HVTN) is focused on redesigning the RV144 regiment for the "clade C" subtype of HIV that is most prevalent in Southern Africa. HVTN 100 -- an early phase trial of the modified vaccine regimen -- finally launched in South Africa in January 2015. Results are expected in late-2016. If there is a positive outcome, a large-scale clinical efficacy trial, HVTN 702, will start in late-2016 or early-2017. Positive efficacy results could lead to licensure of this vaccine.
The HVTN is also conducting a series of clinical trials in Southern Africa to compare different prime-boost pox-protein vaccine regimens and hopefully identify more potent regimens and perhaps an immune correlate. An "immune correlate" is a vaccine-induced immune response such as an antibody or specific type of T cell that is linked to protection from HIV -- the biological marker that tells scientists why the vaccine works. Finding an immune correlate for an AIDS vaccine could help scientists focus research, shorten trials, bring down costs, and guide regulatory and policy decisions in the future.
In addition, the US Military HIV Research Program, the research group that conducted RV144 in Thailand, has conducted follow-up trials and is planning a series of additional clinical trials to build upon the RV144 results in the Thai population. An efficacy trial of an improved RV144 regimen for the Thai population could begin in 2018.
Lessons Learned About Vectors
Three of the previous efficacy trials tested a vaccine using the Adenovirus 5, or Ad5, vector. Early clinical results looked promising, but in the first two efficacy trials, in the United States and South Africa, the vaccine was found to increase some volunteers' risk of infection (this was seen particularly in uncircumcised men with pre-existing antibodies to Ad5). Both trials were stopped immediately. The third trial went forward but excluded uncircumcised men with pre-existing antibodies to Ad5 to reduce potential risk. While it did not find the same increased risk of infection, it also did not find efficacy. Ad5 is no longer considered for AIDS vaccine development.
Other vaccines using different types of adenovirus vectors are being tested, with careful attention to safety throughout the trials. In 2015, Johnson & Johnson and other partners are beginning a Phase I/II trial of a vaccine strategy that uses an "alternative" adenovirus vector and a mosaic immunogen (i.e., one which contains genetic material from many subtypes of HIV, in hopes of providing cross-clade protection).
Broadly Neutralizing Antibodies
Most licensed vaccines induce antibodies that neutralize (render harmless) the virus or other pathogen in question. Scientists have identified numerous broadly neutralizing antibodies (bNAbs) that occur naturally in a number of people with HIV. These bNAbs are potent against many strains of HIV even though they don't control the individual's own virus, which mutates away from the body's most effective responses. Scientists are studying whether these types of bNAbs might provide protection for HIV-negative individuals. Scientists have learned how to engineer bNAbs in the lab and are beginning small trials to give them directly to people as part of a process called "passive immunization". Passive immunization is the transfer of pre-made antibodies to a person, as opposed to teaching a person's immune system to make the antibodies itself, which is how vaccines work. This is the first step to evaluating whether such antibodies could prevent HIV in HIV-negative people.
What Else Is in the Pipeline for AIDS Vaccines of the Future?
There are a range of candidates in early stages of development, and a wide range of basic scientific work (work not focused on product development) ongoing in the AIDS vaccine field. For a description of current and emerging research, see www.avac.org/vaccines. Visit www.avac.org/pxrd for a table of trials and www.avac.org/globalmap for a view to where AIDS vaccine and other biomedical HIV prevention research is ongoing.
Vaccine Advocacy in AVAC Report 2014/15: Prevention on the Line
Check out vaccine-related goals and other important elements of the vaccine and antibody research agendas at http://www.avac.org/resource/avac-report-201415-hiv-prevention-line.
Resources and Links
This article was provided by AVAC: Global Advocacy for HIV Prevention. Visit AVAC's website to find out more about their activities and publications.
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