Early Advances in mRNA-Based HIV Vaccine Strategies from Dual Studies

Recent research efforts employing mRNA technology are showing promising early results in the development of HIV vaccines. HIV vaccine development has traditionally faced obstacles due to the virus's high variability and the challenge of inducing effective neutralizing antibodies. Most existing approaches focus on soluble HIV-1 envelope glycoprotein (Env) trimers that mimic the virus's surface spikes. Despite inducing some antibody responses, many candidates fail to produce broadly neutralizing antibodies, mainly targeting non-essential parts of the Env structure.

Two new influential studies published in Science Translational Medicine have explored the potential of mRNA vaccines encoding stabilized Env trimers. Led by scientists from the Scripps Research Institute, these studies aimed to better direct immune responses toward the critical viral entry sites rather than nonneutralizing targets. They compared soluble and membrane-bound forms of the mRNA-encoded Env trimer (BG505 MD39.3) and found that membrane-anchored versions elicited more potent and durable neutralizing antibodies in animal models such as rabbits and rhesus macaques.

The membrane-bound mRNA vaccines prompted strong T cell responses, including CD4+ and CD8+ populations, with persistent plasma cells observed up to a year later, indicating long-lasting immune memory. Moreover, a phase 1 human trial at the Fred Hutchinson Cancer Center demonstrated that such vaccines could safely induce neutralizing antibodies in HIV-negative adults. In this trial, three doses of membrane-anchored Env trimer mRNA vaccines produced neutralizing responses in 80% of participants, with responses increasing after the second and third doses and remaining detectable for at least six months.

Although adverse effects such as mild to moderate urticaria were noted, most resolved with treatment. The research emphasizes that while these vaccines currently induce strain-specific antibodies, they denote significant progress toward more effective HIV vaccines utilizing mRNA technology. Further research aims to broaden the immune response to achieve coverage across more HIV strains.

This evolving field suggests that mRNA vaccines offer a versatile and powerful platform to combat complex viruses like HIV, with ongoing studies striving for broader, more universal protection.