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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 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 HIV vaccine to prevent infection in HIV-negative people for over 30 years. They have made significant discoveries about HIV, the immune system and vaccinology (the science of vaccine development). 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 HIV vaccine field?

HIV vaccine development has proven extremely challenging. HIV comes in many varieties, mutates rapidly, and 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 successfully eliminated an invading pathogen. Since no human to date has eliminated HIV using their own immune system, scientists cannot employ that strategy.

Proof of concept that an HIV vaccine can reduce risk of infection

Five different HIV 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. This 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 found on the outer surface of the virus. RV144 results were the first proof of concept that a preventive HIV vaccine was possible, and represented 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 developing a vaccine for licensure.

The P5 Initiative

An international consortium known as the Pox-Protein Public Private Partnership (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 regimen 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—is ongoing as of May 2016. Preliminary data is being examined to determine if immune responses in HVTN 100 merit moving this candidate forward to an efficacy trial. If positive, the large-scale clinical efficacy trial, HVTN 702, is expected to start in late 2016. 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 similar regimens made up of different vaccine components and delivery mechanisms with the aim of identifying 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 HIV vaccine could help scientists focus research, shorten trials, bring down costs, and guide regulatory and policy decisions in the future.

The US Military HIV Research Program, the research group that conducted RV144 in Thailand, is conducting a series of additional clinical trials to build upon the RV144 results in the Thai population.

Lessons learned about vectors

Many HIV vaccines use a viral vector, or an alternate virus that will not cause disease, but will help deliver the vaccine components to immune cells more effectively. Some vaccines use combinations of vectors.

In 2015, Johnson & Johnson and other partners launched a series of Phase I/II trials of a vaccine strategy that uses an Adenovirus 26 (Ad26) vector. This research program also involves a Modified Vaccinia Ankara (MVA) vector, a commonly used vector for vaccine candidates, and significantly, a mosaic immunogen, i.e., one which contains genetic material from many subtypes of HIV, in hopes of providing cross-clade protection. A global efficacy trial of this vaccine candidate is set to begin in 2017.

Recently, monkey studies have shown promising results for the vesicular stomatitis virus (VSV) and cytomegalovirus (CMV) vectors. These replicating vectors are being considered for human trials since it is hoped they will provide more durable and potent immune responses. The CMV vector is unique in that, unlike all of the other current vaccine candidates, it only produces a T-cell response.

Safety remains a key focus of vector selection. Three of the previous efficacy trials tested a vaccine using the Adenovirus 5 (Ad5) vector. Early clinical results looked promising, but in the first two efficacy trials, in the US 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). Ad5 is no longer considered for HIV vaccine development.

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 to give them directly 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. Researchers have begun to put bNAbs into clinical trials. Furthest along in the pipeline is the bNAb known as VRC01; two proof of concept studies of passive immunization with VRC01 are beginning in the first half of 2016.

What else is in the pipeline for HIV vaccines of the future?

There is a range of early development and basic scientific work ongoing in the HIV vaccine field. For a description of emerging research, see www.avac.org/vaccines. Visit www.avac.org/pxrd for a table of trials and www.avac.org/globalmap for a visual of where vaccine and other biomedical HIV prevention research is ongoing.

Last updated May 2016.