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The Basics

This fact sheet provides basic information on preventive HIV vaccines. For additional materials on the status of HIV vaccine research, visit our HVAD section. For more basic fact sheets in this series on emerging HIV prevention strategies visit www.avac.org/intro.

What is an HIV vaccine?

A preventive HIV vaccine would teach the immune system how to create protective immune responses that blocked the virus from establishing infection in HIV-negative people. Scientists have been looking for an HIV vaccine t for over 30 years. They have made significant discoveries about HIV, the immune system and vaccinology in general. But no HIV vaccine exists today.

Scientists are also developing therapeutic vaccines. These would build immune strength in HIV-positive people and thereby reduce their risk of getting sick and, ideally, their reliance on antiretroviral treatment. Therapeutic vaccines may also play a part in a strategy to find a cure. (see www.avac.org/blog/therapeutic-vaccines). This factsheet concentrates on preventive vaccines being developed for use by HIV-negative people.

What are some of the key developments in the HIV vaccine field?

HIV vaccine development has proven extremely challenging. There are several genetic subtypes, or families of HIV, each of which may require a specific vaccine. The virus mutates rapidly, allowing it to evade the body’s defenses. It primarily attacks the very cells needed to mount an effective immune response. Most effective vaccines against other pathogens 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.

What is the status of HIV vaccine research?

Five HIV vaccine efficacy trials failed to show any impact on preventing infection. But in 2009 a trial called RV144 released showed that those who received the vaccine were 31 percent less likely overall to acquire HIV than those who received placebo. The RV144 vaccine regimen was a combination “prime-boost” vaccine, which required six injections over a six-month period. RV144 used a canary pox as a vector to introduce a non-infectious particle of HIV. Called ALVAC, the vaccine was intended to “prime” the immune system. The “boost” was a manufactured protein modeled after the gp120 protein on the outer surface of the HIV virus. RV144 results were the first proof of concept that a preventive HIV 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. Since that trial, the field has worked to improve on it—while pursuing other strategies.

Who is following up on the RV144 result?

An international consortium known as the Pox-Protein Public Private Partnership (or P5) is working together to examine whether changing the RV144 vaccine regimen could result in greater efficacy, for example, replacing the protein with a better formulation of gp120, increasing the number of “boosts”, or adding an “adjuvant”—a substance to increase the body’s response to the vaccine.

The HIV Vaccine Trials Network (HVTN) has redesigned the RV144 regiment for the type of HIV that is most prevalent in Southern Africa, known as subtype “clade C”. Results from HVTN 100—an early phase trial tested the modified vaccine regimen. In May, 2016, NIH announced that HVTN 100 had met its “go” criteria to move forward with a large-scale clinical efficacy trial—HVTN 702—to 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, comparing different regimes for prime-boost pox-protein vaccines. Hopefully, these trials will identify a potent regime with an “immune correlate”, a vaccine-induced immune response such as an antibody or specific type of T cell—these biological markers can tell scientists why a 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 building on the RV144 results in the Thai population, including an efficacy trial expected in 2018.

What are the other trends in vaccine research?

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. In the summer 2016 HIV the HVTN and the HIV Prevention Trials Network (HPTN) began recruitment for the “AMP” (Antibody-Mediated Prevention) trial. AMP will measure the safety and effectiveness of an intravenous infusion of the broadly neutralizing antibody VRC01 for HIV prevention. AMP consists of two parallel trials. One, in sites across Brazil, Peru and the US, recruited men and transgender people who have sex with men. The other study will enroll women in sites across Botswana, Kenya, Malawi, Mozambique, South Africa, Tanzania and Zimbabwe.

The vaccine pipeline

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.

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 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 began 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).

Vaccine advocacy in AVAC Report 2016: Big Data, Real People

Check out vaccine-related goals and other important elements of the vaccine and antibody research agendas at www.avac.org/report2016.

Last updated September 2016.