W26052102 Imbokodo & Mosaico updates, plans for correlates and sieve analyses.

Summary

The script discusses an extensive public-private partnership working on a global prophylactic HIV vaccine. The goal is to develop a vaccine effective against diverse HIV strains, using mosaic antigen designs. Two ongoing efficacy studies, Imbokoto and Mosaico, are evaluating the vaccine in different populations and transmission modes. The studies involve immunogenicity evaluations, sieve analysis, and immune bridging to support a broad evidence package. The aim is to identify immune markers associated with vaccine efficacy and understand how and where the vaccine could be used globally.

Takeaways

• 🌐 The program aims to develop a global prophylactic vaccine for HIV, targeting diverse strains worldwide, not just strain or plate-specific vaccines.
• 🔬 Mosaic antigen designs by Betty Gorber are central to the vaccine development, using a heterologous regimen for delivery.
• 📚 Two ongoing efficacy studies, Imbokoto and Mosaico, are complementary and focus on different HIV clades and transmission modes.
• 📊 Imbokoto is conducted in Southern Africa with a focus on clade C viruses, while Mosaico evaluates in the Americas and Europe, focusing on clade B.
• 👥 The studies involve different demographics: Imbokoto targets young women (18-35), whereas Mosaico includes MSM and transgender individuals (18-60).
• 💉 The vaccine regimen involves multiple vaccinations with different components to enhance immune responses against various HIV strains.
• 🧬 Sieve analysis is being conducted to understand the vaccine's effect on viral gene sequences and to identify mechanisms of an imperfect vaccine regimen.
• 🔄 Immunobridging studies are necessary to connect the efficacy of the vaccine regimens across different studies and populations.
• 📈 A pilot immunogenicity study is underway in the Imbokoto study to characterize vaccine responses in the study population and identify potential predictors of immune responses.
• 🧬 Future immune and correlates analyses in the Mosaico study will build upon the findings and learnings from the Imbokoto study.
• 🌟 The ultimate goal is to identify strong immunologic markers associated with vaccine efficacy, which could help define the use of such vaccines globally.

Q & A

What is the primary goal of the HIV vaccine program mentioned in the transcript?

The primary goal of the program is to develop a global prophylactic vaccine that is not strain or plate-specific but is relevant for the globally diverse strains of HIV, based on mosaic antigen designs.

Who developed the mosaic antigen designs used in the vaccine?

Betty Gorber developed the mosaic antigen designs used in the vaccine.

What is the significance of a heterologous vaccine regimen in the context of this program?

A heterologous vaccine regimen is used to deliver the mosaic antigens and for Gag, Pol, and Env, which are coated by Ad26, as well as soluble trimeric gp-140, to enhance the vaccine's efficacy.

What are the two ongoing efficacy studies mentioned in the transcript?

The two ongoing efficacy studies are the Imbokoto study, which uses the vaccine HBTN705, and the Mosaico study, which uses the vaccine HBTN706.

In which regions are the Imbokoto and Mosaico studies taking place?

The Imbokoto study is taking place in five countries in Southern Africa, while the Mosaico study is conducted throughout the Americas and Europe.

What is the predominant virus clade circulating in the Impacto study?

Clade C is the predominant virus circulating in the Impacto study.

What are the differences in the study designs between Imbokoto and Mosaico?

Both studies have a similar design with a one-to-one randomization and participants receiving two vaccinations. The difference is that in Mosaico, the third and fourth vaccinations also include the mosaic gp-140 component to expand immune responses.

What is the purpose of the immunobridging studies mentioned in the transcript?

The immunobridging studies aim to support a broad evidence package for the use of the vaccines by bridging between different vaccine regimens, populations, and plates to show the vaccine's efficacy across various conditions.

What are the objectives of the pilot immunogenicity study currently taking place in the Imbokoto study?

The pilot immunogenicity study aims to characterize the immunogenicity of the vaccine regimen in the study population, understand the temporal relationships between immune responses, and develop predictors of immune responses to inform future analyses.

What is the sieve analysis, and how does it contribute to the vaccine program?

The sieve analysis involves sequencing all viral genes encoded in the vaccine to characterize differences between virus sequences in the study arms. It helps elucidate the mechanisms of an imperfect vaccine regimen and guides future iterations and hypotheses for immune correlance analyses.

How do the results from the Imbokoto study plan to inform the Mosaico study?

The results from the Imbokoto study will allow for the definition and testing of specific correlates hypotheses in the Mosaico study, helping to identify immune markers associated with risk of infection and defining the use of the vaccine.

What is the hypothesis regarding the extrapolation of vaccine efficacy to other HIV clades?

The hypothesis is that if efficacy can be demonstrated and similar levels of immune responses are seen across clades, then the vaccine could also prevent infection by other diverse strains of HIV, which needs to be supported by strong immunologic markers associated with vaccine efficacy.