An Effective HIV Vaccine May Be on the Horizon

With the first cases of what would eventually become known as AIDS emerged in the United States in 1981, the country was unknowingly entering into an epidemic. At the time, small pockets of young, previously healthy men had cropped up with rare diagnoses in both New York and California; cases of a rare lung infection known as Pneumocystis carinii pneumonia (PCP) and a rare, aggressive cancer known as Kaposi’s Sarcoma highlighted a potential immunodeficiency problem in these populations. Cases of PCP emerged in unrelated groups of intravenous drug users later that year, resulting in nearly 300 cases of this unknown immunodeficiency and 121 deaths.

By the time the CDC gave the acquired immunodeficiency syndrome (AIDS) epidemic an official name at the end of 1982, it’s likely that as many as 300,000 people may have been infected on six continents. Two years later, researchers identified HTLV III/LAV – now known as HIV – as the antigen responsible for AIDS. Since then, the virus has been the subject of much research in an effort to produce a vaccine that could prevent or cure AIDS. While AIDS treatment has taken great strides in recent decades, HIV vaccines have been largely disappointing – until now.

Antibody Discovery and HIV

In general, to develop any vaccine, researchers must first discover potential antibodies that may work to neutralize an antigen target. The process, known as antibody discovery, is typically based on utilizing recombinant DNA technology to produce monoclonal antibodies (maB) within living cells. Researchers use microplate dispensers to isolate antibodies before producing antibody cell lines for further study of a single antibody against a particular antigen.

Ideally, antibodies are used to develop a vaccine that will mimic the presence of the antigen itself, generating a response from the B-cells of the immune system to produce the proper antibodies needed to fight it. However, HIV has proven extremely resistant to vaccine development for three key reasons:

1. HIV is genetically variable, resulting in a difficulty in generating a vaccine target each specific virus of origin

2. HIV utilizes glycan shielding to protect its proteins with a thick envelope of sugars that resist antibody bonding

3. HIV mutates as it reproduces and quickly develops resistance to antibodies

bNAbs as Vaccines

A solution to the problems experienced by traditional antibodies could be the use of broadly neutralizing antibodies, or bNAbs. These antibodies are active against a large number of virus strains, meaning that they could attack multiple HIV strains and have additional protein extensions that enable them to pierce the glycan shield to attack HIV. Currently, the National Institutes of Health is reporting human studies that involve utilizing portions of a virus as a vaccine to stimulate production of bNAbs that could eventually attack HIV.

The NIH study utilizes the shell of adenovirus – a virus that produces the common cold – and replaces its genes with DNA that codes for a bNAb shown to be effective against HIV. This bNAb, known as VRC07, does not stimulate the production of opposing antibodies. When given to HIV-positive volunteers, the vaccine was effective in reducing viral load.

A similar Scripps study conducted in monkeys utilizes an envelope protein of HIV itself to stimulate the body to produce a variety of different bNAbs. This protein has been modified to be much more stable than the original HIV protein and generates a better immune response than the original form. In addition, researchers utilized an osmotic pump method of delivery, which involves a small implant designed to slowly release the vaccine over time – such a method prompted production of nearly a thousand times as many bNAbs as previous methods.

Future Implications

As research into bNAbs continues, the future for an HIV vaccine begins to look more and more promising. Researchers may have found a number of methods to attack HIV’s three roadblocks to antibody response. With the further development of these methods, some of which have already entered human trials, scientists may be able to induce the human body to generate antibodies to neutralize HIV – a process the 37.9 million people with HIV worldwide eagerly await.

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