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Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1
- Source :
- Nature medicine. 24(6)
- Publication Year :
- 2018
-
Abstract
- A central goal of HIV-1 vaccine research is the elicitation of antibodies capable of neutralizing diverse primary isolates of HIV-1. Here we show that focusing the immune response to exposed N-terminal residues of the fusion peptide, a critical component of the viral entry machinery and the epitope of antibodies elicited by HIV-1 infection, through immunization with fusion peptide-coupled carriers and prefusion stabilized envelope trimers, induces cross-clade neutralizing responses. In mice, these immunogens elicited monoclonal antibodies capable of neutralizing up to 31% of a cross-clade panel of 208 HIV-1 strains. Crystal and cryoelectron microscopy structures of these antibodies revealed fusion peptide conformational diversity as a molecular explanation for the cross-clade neutralization. Immunization of guinea pigs and rhesus macaques induced similarly broad fusion peptide-directed neutralizing responses, suggesting translatability. The N terminus of the HIV-1 fusion peptide is thus a promising target of vaccine efforts aimed at eliciting broadly neutralizing antibodies. An alternative HIV vaccine design facilitates generation of HIV-1-antibodies, with promising neutralization breadth in rodents and nonhuman primates.
- Subjects :
- 0301 basic medicine
Models, Molecular
Viral protein
medicine.drug_class
Recombinant Fusion Proteins
Guinea Pigs
Peptide
HIV Antibodies
medicine.disease_cause
Monoclonal antibody
General Biochemistry, Genetics and Molecular Biology
Epitope
Neutralization
03 medical and health sciences
Epitopes
0302 clinical medicine
Immune system
Viral entry
Neutralization Tests
medicine
Animals
Amino Acid Sequence
HIV vaccine
030304 developmental biology
chemistry.chemical_classification
AIDS Vaccines
0303 health sciences
biology
env Gene Products, Human Immunodeficiency Virus
General Medicine
Virology
Antibodies, Neutralizing
Macaca mulatta
3. Good health
Mice, Inbred C57BL
030104 developmental biology
Immunization
chemistry
biology.protein
HIV-1
Female
Antibody
Peptides
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 1546170X
- Volume :
- 24
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Nature medicine
- Accession number :
- edsair.doi.dedup.....4676b3f4ae4ed7cf9745702cd741e9d5