With positive results from Phase 1 clinical trials, could the dream of an HIV vaccine finally come true?

Singularityhub.com reports that Red Maple Bay recently published an article titled "The Dream of HIV Vaccines May Finally Be Coming True" Some may find the content too technical and difficult to understand. Therefore, we have translated a more accessible version today to help you better understand this new breakthrough in vaccine development.

Previous HIV vaccine candidates have used antibodies to target the "stem" of Env, engineering mRNA molecules that instruct cells to produce both parts of the Env protein to enhance the immune response. In HIV-infected mice, mRNA vaccines targeting these two parts of the Env protein stimulated antibody production. However, the stem may be hidden within the viral membrane, making it inaccessible to antibodies.

HIV has a protective outer shell called the envelope, which contains a protein called Env. Some versions of this protein are soluble in blood, while others are attached to viral and cell membranes.

mRNA molecules are the part of the virus that mutates most slowly. Cells produce this protein to alert the immune system. Using mRNA, cells produce a small fragment of the virus, teaching the immune system to recognize it as an invader. When infected with the actual pathogenic virus, the body produces antibodies to neutralize it. With HIV, the same strategy protects immune cells from viral invasion, preparing the body for battle.

◆ First New Study

Inspired by the COVID-19 vaccine, two studies are improving HIV vaccine formulations. The new vaccines contain mRNA molecules encoding the HIV "Env stem" and deliver them into cells.

One of the vaccines encodes both soluble and membrane-bound forms of the Env protein. When both versions were injected into animals, they triggered a robust antibody response against HIV.

• When the vaccine was injected into the leg muscles of rabbits, the animals produced antibodies against these proteins for up to 24 weeks. The membrane-bound form was significantly more effective.
• In monkeys, the vaccine significantly reduced HIV levels over 26 weeks and boosted the animals' B cell responses. Immune cells also formed a reservoir of "memory" cells that could be activated upon reinfection with HIV.

◆ Second New Study

Encouraged by these results, a second research team enrolled 108 healthy individuals at 10 sites across the United States to test both versions of the vaccine. This Phase 1 clinical trial primarily studied safety but also monitored antibody responses in volunteers aged 18 to 55.

Each volunteer received three different doses of a single vaccine. Consistent with the animal studies, the membrane-bound version was more effective, blocking HIV in nearly 80% of people. The soluble version was less effective, with only 4% of participants producing antibodies.

The overall impact of the vaccine on the body was minimal. However, approximately 6.5% of participants, regardless of dose, developed a large rash, some of which persisted for years. This reaction may be due to a combination of HIV infection and a side effect of the mRNA. The research team is still investigating the exact mechanism that causes the rash and how to address it.

Expert Opinion

William Schief's team at the Scripps Research Institute stated that while these vaccines are not perfect, they are relatively easy to distribute and administer. They also revealed how different versions of the protein affect immunity: a membrane-bound version had a particularly significant effect. These results "should aid in HIV vaccine development."

Sharon Lewin of the Peter Doherty Institute for Infection and Immunity told Nature that the differences between membrane-bound and soluble vaccines are significant. With nearly 41 million people living with HIV worldwide, the need for an HIV vaccine is significant, and side effects are only a minor obstacle in the development process.