HIV Vaccine Candidate Triggers Essential Antibodies in Humans, Shows Early Success in Clinical Trial

An experimental HIV vaccine developed at the Duke Human Vaccine Institute shows the ability to trigger low levels of an elusive type of neutralizing antibodies in a small group of participants.

Potent But Elusive Antibody

In order for immunization to work, it needs to raise antibodies in the vaccinated individual, or those that are primed to neutralize potential intruders. For a vaccine to be safe, on the other hand, it needs to demonstrate this ability without major side effects or reactions.

A type of antibody, called broadly neutralizing antibodies (bNAbs) has the ability to recognize and block the entry of a broad range of various strains of HIV into healthy cells. This protein was discovered in the early 1990s at the peak of the HIV/AIDS epidemic.

Right after their discovery, the potential of bNAbs was immediately recognized. They can target and neutralize multiple strains of HIV despite their ability to shuffle their outer coat to avoid immune detection.

Despite almost four decades of research, however, experts still face the challenge of developing a vaccine that can generate bnAbs in humans, let alone any vaccine for HIV. After all, it is not easy to command the immune system to create bnAbs since these potent antibodies materialize in 10-25% of people living with HIV, and they can take years to develop successfully.

HIV Vaccine Candidate

A team of scientists achieved a significant milestone in HIV research after developing a vaccine that can stimulate the production of bnAbs. The details of the study were discussed in the paper "Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans."

The experimental HIV vaccine targets the membrane-proximal (MPER), which is an area on the HIV-1 outer envelope. This envelope has the ability to remain stable even as the virus mutates. Antibodies against MPER can block the viral infection by various circulating strains of HIV.

In this study, 21 HIV-negative individuals were enrolled in the trial. Fifteen of them received two of four planned doses, while five received three doses. The broadly neutralizing antibodies were induced in the participants after only two doses.

After two immunizations, the vaccine demonstrated a 95% serum response rate and a 100% blood CD4+ T-cell response rate. These are both vital instruments to show strong immune activation.

The vaccine also features other promising capabilities, such as maintaining the crucial immune cells in a state of development that enables them to continue acquiring mutations. This allows them to evolve along with the ever-changing HIV.

According to senior author Barton F. Haynes, their study is a major step forward by demonstrating the possibility of inducing antibodies with immunizations that neutralize the most challenging HIV strains. The team also plans to induce more potent bnAbs against other sites on HIV to avoid virus escape.

Haynes and his colleagues recognize that there is still more work to be done in order to target more regions of the virus envelope and to develop a more robust response. A successful vaccine against HIV will likely have at least three components, which are all aimed at well-defined regions of the virus.

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