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| Title | Anti-immune complex antibodies are elicited during repeated immunization with HIV Env immunogens. |
|---|---|
| Journal, issue, pages | Sci Immunol, Vol. 10, Issue 103, Page eadp5218, Year 2025 |
| Publish date | Jan 17, 2025 |
 Authors | Sharidan Brown / Aleksandar Antanasijevic / Leigh M Sewall / Daniel Montiel Garcia / Philip J M Brouwer / Rogier W Sanders / Andrew B Ward /    |
| PubMed Abstract | Vaccination strategies against HIV-1 aim to elicit broadly neutralizing antibodies (bnAbs) using prime-boost regimens with HIV envelope (Env) immunogens. Epitope mapping has shown that early antibody ...Vaccination strategies against HIV-1 aim to elicit broadly neutralizing antibodies (bnAbs) using prime-boost regimens with HIV envelope (Env) immunogens. Epitope mapping has shown that early antibody responses are directed to easily accessible nonneutralizing epitopes on Env instead of bnAb epitopes. Autologously neutralizing antibody responses appear upon boosting, once immunodominant epitopes are saturated. Here, we use electron microscopy-based polyclonal epitope mapping (EMPEM) to elucidate how repeated immunization with HIV Env SOSIP immunogens results in the generation of Ab2α anti-idiotypic antibodies in rabbits and rhesus macaques. We present the structures of six anti-immune complex antibodies and find that they target idiotopes composed of framework regions of antibodies bound to Env. Examination of cryo-electron microscopy density enabled prediction of sequences for an anti-immune complex antibody, the paratope of which is enriched with aromatic amino acids. This work sheds light on current vaccine development efforts for HIV, as well as for other pathogens in which repeated exposure to antigen is required. |
 External links | Sci Immunol / PubMed:39823319 |
| Methods | EM (single particle) |
| Resolution | 3.3 - 25.0 Å |
| Structure data | EMDB-43838, PDB-9atz:  EMDB-43894: HIV-1 B41 SOSIP.v4.1 Env in Complex with N241 Epitope and Anti-Immune Complex Antibodies  EMDB-43895: nsEM of HIV-1 16055 SOSIP.v8.3 Env in Complex with Week 6 Base pAb (Rabbit ID: 2464)  EMDB-43896: nsEM of HIV-1 16055 SOSIP.v8.3 Env in Complex with Week 22 N611, V2, and Base Epitope pAbs (Rabbit ID: 2464) EMDB-43935, PDB-9axd: EMDB-43967, PDB-9axi: EMDB-43968, PDB-9axk: EMDB-43981, PDB-9ay6: EMDB-43998, PDB-9ays: EMDB-43999, PDB-9ayv:  EMDB-44076: nsEM of HIV-1 BG505 SOSIP.v5.2 (N289/N241) Env in Complex with Week 38 gp120-Interface, N289, C3/V5, Base, and Anti-Immune Complex Epitope pAbs (NHP ID: Rh33203) |
| Chemicals |  ChemComp-NAG:  ChemComp-MAN: |
| Source |
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 Keywords | VIRAL PROTEIN / HIV / Polyclonal / Antibodies / CryoEMPEM / Rabbit / Anti-Immune Complex / V1/V3 / NHP / Macaque / gp120-Interface / EMPEM / Polyclonal Antibodies / N625 / Base / SOSIP / N611 / V5 |
oryctolagus cuniculus (rabbit)
human immunodeficiency virus 1
macaca mulatta (Rhesus monkey)