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Protection of neonatal macaques against experimental SHIV infection by human neutralizing monoclonal antibodies.

Publication ,  Journal Article
Ruprecht, RM; Hofmann-Lehmann, R; Smith-Franklin, BA; Rasmussen, RA; Liska, V; Vlasak, J; Xu, W; Baba, TW; Chenine, AL; Cavacini, LA; Rizvi, TA ...
Published in: Transfus Clin Biol
August 2001

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.

Duke Scholars

Published In

Transfus Clin Biol

DOI

ISSN

1246-7820

Publication Date

August 2001

Volume

8

Issue

4

Start / End Page

350 / 358

Location

France

Related Subject Headings

  • Virus Shedding
  • Virus Assembly
  • Vaccination
  • Species Specificity
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Pregnancy Complications, Infectious
  • Pregnancy
  • Pilot Projects
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ruprecht, R. M., Hofmann-Lehmann, R., Smith-Franklin, B. A., Rasmussen, R. A., Liska, V., Vlasak, J., … McClure, H. M. (2001). Protection of neonatal macaques against experimental SHIV infection by human neutralizing monoclonal antibodies. Transfus Clin Biol, 8(4), 350–358. https://doi.org/10.1016/s1246-7820(01)00187-2
Ruprecht, R. M., R. Hofmann-Lehmann, B. A. Smith-Franklin, R. A. Rasmussen, V. Liska, J. Vlasak, W. Xu, et al. “Protection of neonatal macaques against experimental SHIV infection by human neutralizing monoclonal antibodies.Transfus Clin Biol 8, no. 4 (August 2001): 350–58. https://doi.org/10.1016/s1246-7820(01)00187-2.
Ruprecht RM, Hofmann-Lehmann R, Smith-Franklin BA, Rasmussen RA, Liska V, Vlasak J, et al. Protection of neonatal macaques against experimental SHIV infection by human neutralizing monoclonal antibodies. Transfus Clin Biol. 2001 Aug;8(4):350–8.
Ruprecht, R. M., et al. “Protection of neonatal macaques against experimental SHIV infection by human neutralizing monoclonal antibodies.Transfus Clin Biol, vol. 8, no. 4, Aug. 2001, pp. 350–58. Pubmed, doi:10.1016/s1246-7820(01)00187-2.
Ruprecht RM, Hofmann-Lehmann R, Smith-Franklin BA, Rasmussen RA, Liska V, Vlasak J, Xu W, Baba TW, Chenine AL, Cavacini LA, Posner MR, Katinger H, Stiegler G, Bernacky BJ, Rizvi TA, Schmidt R, Hill LR, Keeling ME, Montefiori DC, McClure HM. Protection of neonatal macaques against experimental SHIV infection by human neutralizing monoclonal antibodies. Transfus Clin Biol. 2001 Aug;8(4):350–358.
Journal cover image

Published In

Transfus Clin Biol

DOI

ISSN

1246-7820

Publication Date

August 2001

Volume

8

Issue

4

Start / End Page

350 / 358

Location

France

Related Subject Headings

  • Virus Shedding
  • Virus Assembly
  • Vaccination
  • Species Specificity
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Pregnancy Complications, Infectious
  • Pregnancy
  • Pilot Projects