Tracking Mosaico, mRNA, and Broadly Neutralizing Antibody Vaccines
After 40 years of research and over $100 billion invested, an effective HIV vaccine remains elusive. HIV's rapid mutation rate, integration into host DNA, and ability to establish latent reservoirs present unique challenges. Previous Phase 3 trials (RV144, HVTN 702, HVTN 705 "Imbokodo") showed limited efficacy or were discontinued. Current efforts focus on multiple strategies: Mosaico (mosaic adenovirus vectors targeting diverse HIV strains), mRNA vaccines (applying COVID-19 vaccine technology), broadly neutralizing antibodies (bNAbs targeting conserved viral epitopes), and therapeutic vaccines (inducing HIV remission in infected individuals). While no preventive vaccine is approved, combinations of these approaches plus advances in immunology offer renewed hope.
Developer: Janssen Pharmaceuticals (Johnson & Johnson) / HVTN
Platform: Mosaic adenovirus 26 (Ad26) vector prime + clade C gp140 protein boost
Target Population: Men who have sex with men and transgender individuals in Europe and Americas
Design: Tetravalent mosaic immunogens designed to induce broad immune responses against diverse HIV-1 strains
Status: Phase 2b/3 trial (HVTN 706) launched 2019, enrolling 3,800 participants across 8 countries (USA, Brazil, Argentina, Italy, Poland, Spain, Peru, Mexico). Primary endpoint: prevention of HIV infection. Trial ongoing with results expected 2024-2025.
Background: Uses "mosaic" approach combining HIV sequences from multiple clades to provide broader coverage than previous single-clade vaccines.
Developer: Imperial College London / African partners
Platform: DNA prime + MVA (modified vaccinia Ankara) boost encoding CN54 HIV-1 immunogens
Innovation: First trial combining PrEP (pre-exposure prophylaxis) with vaccine
Status: Phase 2b/3 trial in Uganda and Tanzania, enrolling 1,668 participants. Comparing vaccine alone, PrEP alone, and combination. Evaluating whether vaccine can reduce PrEP pill burden.
Rationale: Combination approach may provide better protection than either intervention alone, with potential for reduced PrEP dosing requirements.
Developer: Moderna / IAVI (International AIDS Vaccine Initiative)
Platform: mRNA platform encoding HIV envelope proteins
Goal: Prime B cells to generate broadly neutralizing antibodies (bNAbs) targeting conserved HIV epitopes
Innovation: Uses "germline targeting" approach to guide immune system toward producing rare bNAbs that can neutralize diverse HIV strains
Status: Phase 1 trial (IAVI G002) completed 2023, showed successful B cell priming in 97% of participants. Phase 2 trials expanding. Building on success of mRNA COVID-19 vaccine platform.
Developer: Vir Biotechnology
Platform: Long-acting broadly neutralizing antibody (bNAb)
Mechanism: Monoclonal antibody targeting HIV envelope protein, preventing viral entry
Goal: Provide passive immunity with 6-12 month protection from single injection
Status: Phase 2 trials evaluating safety, pharmacokinetics, and efficacy. Could complement or substitute for daily PrEP pills.
Developer: Scripps Research / IAVI
Platform: Protein nanoparticle designed to activate rare B cell precursors
Innovation: "Germline targeting" - trains immune system through sequential immunizations to produce bNAbs
Status: Phase 1 trial showed 97% of participants developed targeted B cells. Advancing to Phase 2 with booster components.
Goal: Induce HIV remission in infected individuals (functional cure)
Approaches:
Status: Multiple Phase 1/2 trials ongoing. Some show enhanced immune control of HIV replication off antiretroviral therapy, but sustained remission remains rare.
Developer: Janssen / HVTN
Status: Follow-up to HVTN 705 "Imbokodo" trial (discontinued 2021)
Platform: Similar Ad26 mosaic approach with modifications
Note: Learning from previous trial to optimize immunogen design and dosing schedules.
Developer: Duke University / NIAID
Platform: Consensus HIV envelope trimer protein
Goal: Induce broadly neutralizing antibodies through stabilized envelope protein presentation
Status: Phase 1 safety and immunogenicity trials ongoing.
HIV vaccine development faces unprecedented challenges: extreme viral diversity (>70 million variants per person), rapid mutation (>10,000x faster than influenza), integration into host DNA creating latent reservoirs, and destruction of CD4+ T cells (the cells that coordinate immune responses). The virus also uses glycan shields to hide conserved epitopes from antibodies. No previous HIV vaccine trial has shown >50% efficacy. However, advances in structural biology, computational design, and mRNA technology provide new tools. The path forward likely involves combinations of approaches: bNAbs for passive protection, germline-targeting vaccines for active immunity, and therapeutic vaccines to achieve functional cure.