Investigating the Protein Dose-Sparing Effect of AS01B Adjuvant in a Subtype C gp120 HIV Vaccine Trial

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In a recent phase1/2a randomized preventive HIV vaccine trial, Zvavahera (Mike) Chirenje, M.D., of the Bixby Center for Global Reproductive Health, and colleagues have identified a protein dose-sparing effect of the AS01B adjuvant. The trial utilized the ALVAC-HIV (vCP2438) vaccine and an adjuvanted bivalent subtype C glycoprotein 120 (gp120) vaccine, providing valuable insights into the potential for improved HIV prevention strategies.

Protein dose-sparing is a technique that aims to maximize the efficiency of vaccine production by reducing the amount of antigen needed in each dose. Antigens are the components of vaccines that stimulate the immune system and generate an immune response. By optimizing the formulation and delivery of vaccines, protein dose-sparing can help stretch the limited vaccine supply and reach more people.

Adjuvants are substances that are added to vaccines to enhance the immune response. They work by stimulating the immune system, allowing for a stronger and more effective reaction to the vaccine. One of many obstacles in HIV vaccine research has been finding adjuvants that can elicit a durable and strong immune response.

Known for producing robust antigen’s specific antibody responses in humans, the AS01B adjuvant contains two immunostimulants, a toll-like receptor 4 agonist from Salmonella minnesota and a natural saponin molecule from the bark of a South America tree Quillaja saponaria. The same adjuvant is part of the herpes zoster vaccine known as Shingrix. These same components are also utilized in the recently approved RSV vaccine, Arexvy, but under the name AS01E.

The randomized, double-blinded, placebo-controlled study involved 160 HIV-negative participants in the United States and sub-Saharan Africa, with 150 receiving the vaccine and 10 receiving a placebo. Each randomized group received either a high dose of the ALVAC-HIV (vCP2438) vaccine alone or a lower dose of the vaccine combined with the AS01B adjuvant or another adjuvant, MF-59.

The results of the study published in October 2023 in the Journal of Infectious Diseases demonstrated that the AS01B-adjuvanted groups had higher CD4+ T-cell response rates and magnitudes compared to the MF59-adjuvanted group at months 6.5 and 12. Additionally, at month 12, the 40μg gp120/AS01B group had higher HIV-specific envelope protein-gp120 binding antibody response levels compared to the two 200μg gp120 groups.

This finding might have significant implications for HIV vaccine development. By utilizing the AS01B adjuvant, it may be possible to reduce the amount of antigen required while still achieving a robust immune response. This attribute would not only increase the availability and accessibility of the vaccine but also reduce future production costs.

The protein dose-sparing effect of the AS01B adjuvant could have a profound impact on the global fight against HIV. With approximately 38 million people living with HIV worldwide, an effective and affordable vaccine is essential in curbing the spread of the virus.

Furthermore, the study also demonstrated the safety and tolerability of the vaccine and adjuvant combination. Adverse events were generally mild and transient, highlighting the potential for widespread use in future preventive HIV vaccine campaigns.

It is important to note that this study represents only one step in the complex process of vaccine development. Further research and clinical trials are necessary to validate these findings and ensure the safety and efficacy of the vaccine and adjuvant combination.