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Protection of neonatal macaques against experimental SHIV infection by human neutralizing monoclonal antibodies.
- Source :
-
Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine [Transfus Clin Biol] 2001 Aug; Vol. 8 (4), pp. 350-8. - Publication Year :
- 2001
-
Abstract
- Neonatal macaques were completely protected against oral challenge with SHIV-vpu+, a simian-human immunodeficiency virus that encodes the envelope gene of a laboratory-adapted HIV strain, by pre- and post-natal treatment with a triple combination of human neutralizing monoclonal antibodies (mAbs). The mAbs were directed either against the CD4 binding site, a glycosylation-dependent gp120 epitope, or against a linear epitope on gp41. This triple combination was highly synergistic in vitro and neutralized primary HIV completely. Subsequently, oral challenge was performed with pathogenic SHIV89.6P, an animal-passaged variant of a chimeric virus that encodes the envelope gene of the primary, dual-tropic HIV89.6. Only post-natal treatment with a similar triple mAb combination was used. One out of 4 mAb-treated infants was completely protected from infection. In the other 3 treated animals, there was a tendency towards lower peak viral RNA loads compared with untreated controls. Two out of 4 mAb-treated infants maintained normal CD4+ T-cell numbers, in contrast to all controls that had steep declines at 2 weeks post-challenge. We conclude that the triple mAb combination significantly protected the neonates, even against mucosal challenge with pathogenic SHIV89.6P. Passively administered synergistic human mAbs may play a role in preventing mother-infant transmission of HIV, both against intrapartum transmission as well as against infection through breast milk. As passive immunization is a tool to assess correlates of immune protection, we conclude that the epitopes recognized by the mAbs in our combinations are important for AIDS vaccine development. Future passive immunization studies may reveal other important conserved epitopes.
- Subjects :
- AIDS Vaccines immunology
Administration, Oral
Animals
Animals, Newborn
Antibodies, Monoclonal immunology
CD4 Lymphocyte Count
Cesarean Section
Delivery, Obstetric
Disease Models, Animal
Female
HIV Antibodies immunology
HIV Envelope Protein gp120 immunology
HIV Envelope Protein gp41 immunology
Humans
Immunity, Maternally-Acquired
Infant, Newborn
Infectious Disease Transmission, Vertical prevention & control
Lactation
Macaca mulatta
Maternal-Fetal Exchange
Milk virology
Neutralization Tests
Pilot Projects
Pregnancy
Pregnancy Complications, Infectious virology
Species Specificity
Virus Assembly
Virus Shedding
AIDS Vaccines administration & dosage
Antibodies, Monoclonal administration & dosage
HIV immunology
HIV Antibodies administration & dosage
HIV Infections prevention & control
Immunization, Passive
Simian Acquired Immunodeficiency Syndrome prevention & control
Simian Immunodeficiency Virus immunology
Vaccination
Subjects
Details
- Language :
- English
- ISSN :
- 1246-7820
- Volume :
- 8
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine
- Publication Type :
- Academic Journal
- Accession number :
- 11642027
- Full Text :
- https://doi.org/10.1016/s1246-7820(01)00187-2