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Guiding the long way to broad HIV neutralization
1aInstitute of Medical Microbiology and Hygiene, University RegensburgbInstitute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany.
Current Opinion in HIV and AIDS
|March 4, 2017
Summary
Developing broadly neutralizing antibodies against HIV-1 requires guiding B-cell development. New transgenic mouse models demonstrate that targeting germline B-cell receptors and sequential immunization can achieve this outcome.
Area of Science:
- Immunology
- Vaccine Development
- HIV Research
Background:
- Broadly neutralizing antibodies (bNAbs) are crucial for effective HIV-1 vaccine strategies.
- Achieving bNAbs requires extensive virus diversification and antibody coevolution targeting the HIV-1 envelope protein.
- Current vaccine design focuses on initiating and guiding B-cell development toward bNAb generation.
Purpose of the Study:
- To discuss recent progress in vaccine design approaches for initiating and guiding B-cell development.
- To evaluate these strategies in engineered mouse models expressing human antibodies.
- To demonstrate the feasibility of targeted B-cell development for bNAb induction.
Main Methods:
- Development of specially tailored transgenic mouse strains (knock-in models).
- Engineering mouse models to express human antibody VDJH and VJL loci for specific bNAbs (e.g., VRC01, 3BNC60, PGT121).
- Sequential immunization strategies using carefully selected engineered envelope proteins.
Main Results:
- Transgenic mouse models successfully tested the concept of engaging and guiding B-cell development via sequential immunizations.
- Available models display prerearranged or nonrearranged germline or mature VDJH and VJL loci.
- Data confirm the feasibility of the concept using engineered envelope proteins in knock-in models.
Conclusions:
- Recent studies in knock-in transgenic mouse models provide proof-of-concept for B-cell receptor targeting.
- Sequential immunization following germline B-cell receptor targeting can engage precursor B cells.
- This approach guides B-cell receptor development toward broadly neutralizing reactivity against HIV-1.
