Advances in HIV Vaccine Research Show Promise for Prevention

Affecting millions worldwide, HIV infections are still among the most significant challenges facing global health. Despite notable advances in treatment options, an effective vaccine is urgently needed to prevent new infections and contain the HIV pandemic. In recent years, several promising approaches have emerged from research into vaccines against the HIV virus, focusing on different vaccine platforms and employing innovative strategies.

This article will address the different vaccine platforms and targets; the results of recent clinical trials, such as the Mosaico and Imbokodo studies; the production of broadly neutralizing antibodies (bNAbs) and their results in phase 1 studies; and the potential of messenger ribonucleic acid (mRNA)‑based platforms, based on experience with the COVID‑19 vaccines.

Platforms and Targets

In their search for an effective HIV vaccine, researchers have explored several platforms and targets to generate a robust immune response. These platforms included several viral vectors, protein subunits, DNA, and mRNA. Each option has unique advantages and challenges, but all aim to stimulate the immune system to recognize and neutralize HIV. The mechanism leading to this response occurs in the following forms, depending on the viral platform used:

Viral vector vaccines can use, for example, the adenovirus and the vesicular stomatitis virus and can be genetically modified. They carry HIV‑specific antigens to the host cells, triggering an immune response.
Protein subunit vaccines focus on introducing specific viral proteins to the immune system.
DNA vaccines introduce the DNA of the genetically modified virus to the cells, leading to viral protein production and stimulating an immune response.
mRNA vaccines use the organism's cellular mechanism to produce viral antigens and induce a robust immune response.

In January, Janssen discontinued phase 3 of its investigational HIV vaccine regimen after an independent, scheduled review determined that it was not effective in preventing HIV infection, compared with placebo, among study participants. This discontinuation underscores the paucity of prophylactic approaches in the pipeline for HIV, despite several years of research.

The Imbokodo study assessed the preventive vaccine efficacy, safety, and tolerability of a regimen using a mosaic‑based adenovirus type 26 vector in HIV‑seronegative women residing in sub‑Saharan Africa. Similarly, the Mosaico study, conducted on a diverse population of HIV‑1‑seronegative cisgender men and transgender individuals having sex with cisgender men or transgender individuals, assessed the efficacy of a vaccine regimen based on the adenovirus vector and protein subunit approach. This past January, the Mosaico study was terminated because the regimen did not reach the desired efficacy. The failure of these studies means that there are no HIV vaccines in the last evaluation phase or close to the registration stage.

New technologies and nontraditional approaches are highly necessary. Those used in the past have generally focused on the characteristics of predefined protein epitopes. Some viruses, however, such as influenza, SARS-CoV-2, and HIV, can present with greater antigen diversity and significant immune response escape, which makes these strategies unfeasible.

Production of bNAbs

The HIV vaccine will likely have to induce production of broadly neutralizing antibodies, or bNAbs, as they can recognize globally diverse strains of HIV and may prevent infection. One of the major challenges is that production of bNAbs is rare, even during infection. Such bNAbs bind to relatively conserved epitopes on membrane glycoproteins of each pathogen, with features of each antibody allowing binding to a particular epitope. If vaccines could be developed to induce similar bNAbs consistently, preferably in conjunction with broad T cell immunity, protection against these pathogens might be achieved.

At the end of 2022, data from a first‑in-human phase 1 study with 48 participants brought hope to the advancement of new approaches to HIV vaccines. The study utilized a germline-targeting vaccine design, aiming to induce bNAbs. The results show that it was safe and feasible and induced targeted bNAb‑precursor responses in 97% of vaccine recipients at substantial frequencies in each individual. Although there may still be challenges to face — including the high cost of production and the need for repeated injections — production of bNAbs represents a promising path to the development of an effective HIV vaccine.

Immunizing Agents

The notable success of COVID‑19 mRNA vaccines rekindled an interest in using this platform to develop immunizing agents against HIV. This platform has several advantages. It allows vaccines to be developed quickly, modified easily, and to induce robust and long‑lasting immune responses. Moderna is currently creating two mRNA vaccines (both in phase 1) in three different studies. Moderna's mRNA‑1644 vaccines use eOD-GT8 60mer, and the mRNA-1574 vaccine uses several other mRNAs. Both attempt to stimulate the germline cells to induce bNAbs.

The results of these three studies will be available by the end of this year. They will be essential for understanding the role of the new mRNA platform in the production of bNAbs and for ensuring protection against different strains of the HIV virus. By learning from the development of COVID‑19 vaccines, we can speed up the creation of immunizing agents against HIV with increased production of bNAbs. This promising approach gives us new perspectives and significant advances in our fight against HIV.

This article was translated from the Medscape Portuguese Edition.

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