mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies

Science. 2024 May 17;384(6697):eadk0582. doi: 10.1126/science.adk0582. Epub 2024 May 17.


Germline-targeting (GT) HIV vaccine strategies are predicated on deriving broadly neutralizing antibodies (bnAbs) through multiple boost immunogens. However, as the recruitment of memory B cells (MBCs) to germinal centers (GCs) is inefficient and may be derailed by serum antibody-induced epitope masking, driving further B cell receptor (BCR) modification in GC-experienced B cells after boosting poses a challenge. Using humanized immunoglobulin knockin mice, we found that GT protein trimer immunogen N332-GT5 could prime inferred-germline precursors to the V3-glycan-targeted bnAb BG18 and that B cells primed by N332-GT5 were effectively boosted by either of two novel protein immunogens designed to have minimum cross-reactivity with the off-target V1-binding responses. The delivery of the prime and boost immunogens as messenger RNA lipid nanoparticles (mRNA-LNPs) generated long-lasting GCs, somatic hypermutation, and affinity maturation and may be an effective tool in HIV vaccine development.

MeSH terms

  • AIDS Vaccines* / immunology
  • Animals
  • B-Lymphocytes / immunology
  • Broadly Neutralizing Antibodies* / immunology
  • Cross Reactions
  • Female
  • Gene Knock-In Techniques
  • Germinal Center* / immunology
  • HIV Antibodies* / immunology
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / immunology
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV-1* / genetics
  • HIV-1* / immunology
  • Humans
  • Immunization, Secondary*
  • Liposomes
  • Memory B Cells / immunology
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles*
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology
  • Somatic Hypermutation, Immunoglobulin
  • mRNA Vaccines* / immunology


  • AIDS Vaccines
  • Broadly Neutralizing Antibodies
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Lipid Nanoparticles
  • Liposomes
  • Receptors, Antigen, B-Cell
  • mRNA Vaccines