Abstract illustration of HIV virus transforming into a protective shield.

HIV Vaccine Breakthrough: A Bivalent Protein Boost for Future Clinical Trials

Theo Raines in Health & Wellness December 2025 • 4 min read.

"New research paves the way for improved HIV vaccine strategies, focusing on subtypes CR01_AE and B gp120 antigens and a potent adjuvant."

The quest for an effective HIV vaccine has been a long and arduous journey. The RV144 clinical trial in Thailand marked a turning point, demonstrating that a vaccine could indeed reduce the risk of HIV infection, albeit modestly. This trial, which combined an ALVAC-HIV prime with an AIDSVAX B/E gp120 boost, highlighted the potential of targeting specific viral envelope (Env) regions, particularly the V1V2 loops of gp120.

However, the RV144 trial also revealed challenges that needed to be addressed. The production of gp120 proteins in CHO cells was low, and the resulting antigen products were heterogeneous due to cleavage sites in the V1V2 and V3 loops. Recognizing these limitations, researchers have focused on developing new strategies to improve vaccine efficacy.

A recent study detailed in PLoS One outlines the generation and characterization of a bivalent protein boost designed to overcome these challenges. The new approach involves using CHO cells engineered to produce high yields of A244 gp120, combined with a homogenous and uncleaved subtype B gp120 protein to replace the MN strain used in RV144. This innovative bivalent protein is combined with a potent adjuvant, holding promise for future clinical trials.

Developing a Bivalent Protein Boost: Addressing the Challenges

Abstract illustration of HIV virus transforming into a protective shield.

The research focuses on producing stable CHO cell lines that express high levels of HIV-1 Env antigens. Two specific proteins are at the heart of this approach:

A244.AE gp120: This protein is derived from the CRF01_AE subtype, which is highly prevalent in Thailand and other parts of Asia. The CHO cell line was engineered to produce A244.AE gp120 in high yields, addressing the low production levels seen in previous trials. Furthermore, measures were taken to prevent cleavage in the V1V2 loop, ensuring a more homogenous antigen product.

string

6240.B gp120: This protein is based on the subtype B strain, which is common in North America and Europe, as well as parts of Asia. The 6240.B gp120 is designed to replace the MN gp120 used in the RV144 trial. A key modification was made to prevent cleavage in the V3 loop, resulting in a more stable and homogenous protein.

The Future of HIV Vaccines: Building on Promising Results

The development of this bivalent protein boost represents a significant step forward in the search for an effective HIV vaccine. By addressing the limitations of previous approaches and incorporating key insights from the RV144 trial, researchers are paving the way for future clinical trials that could offer improved protection against HIV infection. The emphasis on high-yield production, antigen homogeneity, and potent adjuvants provides a strong foundation for developing a vaccine that elicits robust and durable immune responses. As the world continues to grapple with the HIV/AIDS pandemic, these advancements offer renewed hope for a future where a preventative vaccine is a reality.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

What exactly is the bivalent protein boost and why is it important for an HIV vaccine?

The bivalent protein boost is a combination of two HIV-1 Envelope (Env) antigens: A244.AE gp120, derived from the CRF01_AE subtype prevalent in Thailand and Asia, and 6240.B gp120, based on the subtype B strain common in North America and Europe. It aims to stimulate a broader immune response against different HIV subtypes. This is significant because HIV has many subtypes, and a vaccine effective against multiple subtypes is more likely to provide widespread protection. This bivalent protein is designed to replace the original gp120 found in the RV144 trial.

What is A244.AE gp120 and why is it used in the vaccine?

A244.AE gp120 is an HIV-1 envelope protein derived from the CRF01_AE subtype. It is produced using engineered CHO cells to achieve high yields. It's significant because the CRF01_AE subtype is highly prevalent in Thailand and other parts of Asia, making it a relevant target for a vaccine intended for those regions. Also, steps are taken to prevent cleavage in the V1V2 loop to ensure a more homogenous antigen product, addressing the heterogeneity issues found in prior vaccine development efforts.

What is 6240.B gp120 and how does it improve on previous vaccine approaches?

6240.B gp120 is an HIV-1 envelope protein based on the subtype B strain, common in North America, Europe, and parts of Asia. Its designed to replace the MN gp120 used in the RV144 trial. A key modification prevents cleavage in the V3 loop, resulting in a more stable and homogenous protein. The stability and homogeneity of the protein are critical for eliciting a consistent and effective immune response, enhancing the potential for vaccine success.

What are CHO cells and why are they used in producing the HIV vaccine components?

CHO cells (Chinese Hamster Ovary cells) are used to produce the A244.AE gp120 and 6240.B gp120 proteins. Using these cells allows for high-yield production of the proteins, addressing a limitation of previous HIV vaccine development efforts where protein production was low. This is significant because sufficient quantities of the antigens are needed for effective vaccine manufacturing and subsequent clinical trials.

What is an adjuvant and why is it important in the context of this vaccine?

An adjuvant is a substance added to a vaccine to enhance the immune response. Potent adjuvants are crucial in HIV vaccine development to stimulate robust and durable immune responses. By using a potent adjuvant, the bivalent protein boost aims to improve the effectiveness of the vaccine by ensuring that the immune system recognizes and responds strongly to the A244.AE gp120 and 6240.B gp120 antigens. The use of a potent adjuvant means a better immune response.