IAVI G004 trial: overview of a next generation HIV vaccine

By Carolina Lima | Published on February 5, 2026 | 3 min read


HIV remains one of the most challenging viruses to prevent because it mutates quickly and can hide from the immune system. Even though treatments have improved greatly, creating a vaccine that works against the many versions of HIV has been extremely difficult.

On January 6, 2026, the International AIDS Vaccine Initiative (IAVI)—an international nonprofit organization focused on developing vaccines and antibody‑based tools to stop HIV—published a press release announcing the launch of the IAVI G004 Phase 1 HIV vaccine trial. The first vaccinations were given on December 15, 2025, in South Africa, a country well‑known for its strong HIV research programs and high need for new prevention options.

What is the IAVI G004 trial?

IAVI G004 is an early‑stage (Phase 1) clinical trial studying a new HIV vaccine strategy. The trial focuses on activating the early steps needed to produce broadly neutralizing antibodies (bnAbs)—a special class of antibodies that can target multiple HIV strains.

bnAbs are important because they recognize parts of HIV that stay the same, even when the virus mutates. Previous IAVI studies (G001, G002, G003) showed that it is possible to start bnAb development in humans. G004 continues that progress.

Why is this vaccine approach different?

This vaccine method is different because it doesn’t try to create a full immune response with one shot. Instead, it trains the immune system step by step. According to the IAVI press release, the three vaccine components are given in a specific sequence, allowing the immune system to gradually learn how to produce bnAbs.

ClinicalTrials.gov confirms that each mRNA vaccine in the trial encodes a different HIV immunogen, and each one pushes the immune system forward to the next stage of bnAb development. This staged approach helps guide the right B‑cells more precisely than older, single‑dose vaccine attempts.

How is the vaccine made?

The IAVI G004 vaccine uses Moderna’s mRNA technology, which provides the body with temporary instructions to make specific HIV‑related proteins. These proteins cannot cause infection, but they help the immune system recognize HIV‑like shapes.

According to ClinicalTrials.gov, the trial uses three different mRNA vaccines, each encoding a different HIV immunogen:

• mRNA‑1645‑eODGT8 – introduces a “starter” HIV protein to activate the earliest bnAb‑precursor B cells.
• mRNA‑1645‑CoreG28v2 – push those B cells further along their development pathway.
• mRNA‑1645‑N332GT5 – designed to shape the final stages of bnAb maturation.

These components are delivered in a sequence, not all at once. This sequencing is essential because bnAbs require very specific B‑cell training steps.

Why is the trial important?

The IAVI G004 trial is important because it brings together several advances that have not previously been combined in HIV vaccine research. According to the IAVI press release, this approach is considered one of the most promising strategies to date, largely because intends to guide the immune system step‑by‑step toward bnAb development, one of the most difficult challenges in HIV vaccine science.

The importance of the trial also stems from the global need for new HIV prevention tools. As highlighted in the IAVI press release, millions of new HIV infections continue to occur worldwide every year and existing methods alone are not enough.

It is built on solid scientific evidence, uses cutting‑edge technology and addresses a critical global health need. If successful, it could help bring us closer to a future where an effective HIV vaccine becomes possible —something researchers have been working toward for decades. 

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About the Author – Carolina Lima
Carolina is a specialist in Anaesthesiology with a deep passion for learning and sharing medical knowledge. Dedicated to advancing the field, Dr. Lima strives to bring fresh, evidence-based insights to the medical community. Viewing medicine not merely as a profession but as a lifelong journey of continuous learning, Dr. Lima is committed to making complex information clear, practical, and useful for healthcare professionals around the world.