An adenovirus-simian immunodeficiency virus env vaccine elicits humoral, cellular, and mucosal immune responses in rhesus macaques and decreases viral burden following vaginal challenge

S. L. Buge, E. Richardson, S. Alipanah, P. Markham, S. Cheng, N. Kalyan, Chris J Miller, M. Lubeck, S. Udem, J. Eldridge, M. Robert-Guroff

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Abstract

Six female rhesus macaques were immunized orally and intranasally at 0 weeks and intratracheally at 12 weeks with an adenovirus type 5 host range mutant (Ad5hr)-simian immunodeficiency virus SIV(sm) env recombinant and at 24 and 36 weeks with native SIV(mac251) gp120 in Syntex adjuvant. Four macaques received the Ad5hr vector and adjuvant alone; two additional controls were naive. In vivo replication of the Ad5hr wild-type and recombinant vectors occurred with detection of Ad5 DNA in stool samples and/or nasal secretions in all macaques and increases in Ad5 neutralizing antibody in 9 of 10 macaques following Ad administrations. SIV-specific neutralizing antibodies appeared after the second recombinant immunization and rose to titers > 10,000 following the second subunit boost. Immunoglobulin G (IgG) and IgA antibodies able to bind gp120 developed in nasal and rectal secretions, and SIV-specific IgGs were also observed in vaginal secretions and saliva. T-cell proliferative responses to SIV gp140 and T-helper epitopes were sporadically detected in all immunized macaques. Following vaginal challenge with SIV(mac251), transient or persistent infection resulted in both immunized and control monkeys. The mean viral burden in persistently infected immunized macaques was significantly decreased in the primary infection period compared to that of control macaques. These results establish in vivo use of the Ad5hr vector, which overcomes the host range restriction of human Ads for rhesus macaques, thereby providing a new model for evaluation of Ad-based vaccines. In addition, they show that a vaccine regimen using the Ad5hr-SIV env recombinant and gp120 subunit induces strong humoral, cellular, and mucosal immunity in rhesus macaques. The reduced viral burden achieved solely with an env-based vaccine supports further development of Ad-based vaccines comprising additional vital components for immune therapy and AIDS vaccine development.

Original languageEnglish (US)
Pages (from-to)8531-8541
Number of pages11
JournalJournal of Virology
Volume71
Issue number11
StatePublished - Nov 1997

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Simian immunodeficiency virus
mucosal immunity
Simian Immunodeficiency Virus
Mucosal Immunity
Host Specificity
Macaca
Adenoviridae
Humoral Immunity
viral load
Macaca mulatta
Viral Load
humoral immunity
Cellular Immunity
host range
cell-mediated immunity
Vaccines
vaccines
mutants
secretion
Neutralizing Antibodies

ASJC Scopus subject areas

  • Immunology

Cite this

An adenovirus-simian immunodeficiency virus env vaccine elicits humoral, cellular, and mucosal immune responses in rhesus macaques and decreases viral burden following vaginal challenge. / Buge, S. L.; Richardson, E.; Alipanah, S.; Markham, P.; Cheng, S.; Kalyan, N.; Miller, Chris J; Lubeck, M.; Udem, S.; Eldridge, J.; Robert-Guroff, M.

In: Journal of Virology, Vol. 71, No. 11, 11.1997, p. 8531-8541.

Research output: Contribution to journalArticle

Buge, SL, Richardson, E, Alipanah, S, Markham, P, Cheng, S, Kalyan, N, Miller, CJ, Lubeck, M, Udem, S, Eldridge, J & Robert-Guroff, M 1997, 'An adenovirus-simian immunodeficiency virus env vaccine elicits humoral, cellular, and mucosal immune responses in rhesus macaques and decreases viral burden following vaginal challenge', Journal of Virology, vol. 71, no. 11, pp. 8531-8541.
Buge, S. L. ; Richardson, E. ; Alipanah, S. ; Markham, P. ; Cheng, S. ; Kalyan, N. ; Miller, Chris J ; Lubeck, M. ; Udem, S. ; Eldridge, J. ; Robert-Guroff, M. / An adenovirus-simian immunodeficiency virus env vaccine elicits humoral, cellular, and mucosal immune responses in rhesus macaques and decreases viral burden following vaginal challenge. In: Journal of Virology. 1997 ; Vol. 71, No. 11. pp. 8531-8541.
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abstract = "Six female rhesus macaques were immunized orally and intranasally at 0 weeks and intratracheally at 12 weeks with an adenovirus type 5 host range mutant (Ad5hr)-simian immunodeficiency virus SIV(sm) env recombinant and at 24 and 36 weeks with native SIV(mac251) gp120 in Syntex adjuvant. Four macaques received the Ad5hr vector and adjuvant alone; two additional controls were naive. In vivo replication of the Ad5hr wild-type and recombinant vectors occurred with detection of Ad5 DNA in stool samples and/or nasal secretions in all macaques and increases in Ad5 neutralizing antibody in 9 of 10 macaques following Ad administrations. SIV-specific neutralizing antibodies appeared after the second recombinant immunization and rose to titers > 10,000 following the second subunit boost. Immunoglobulin G (IgG) and IgA antibodies able to bind gp120 developed in nasal and rectal secretions, and SIV-specific IgGs were also observed in vaginal secretions and saliva. T-cell proliferative responses to SIV gp140 and T-helper epitopes were sporadically detected in all immunized macaques. Following vaginal challenge with SIV(mac251), transient or persistent infection resulted in both immunized and control monkeys. The mean viral burden in persistently infected immunized macaques was significantly decreased in the primary infection period compared to that of control macaques. These results establish in vivo use of the Ad5hr vector, which overcomes the host range restriction of human Ads for rhesus macaques, thereby providing a new model for evaluation of Ad-based vaccines. In addition, they show that a vaccine regimen using the Ad5hr-SIV env recombinant and gp120 subunit induces strong humoral, cellular, and mucosal immunity in rhesus macaques. The reduced viral burden achieved solely with an env-based vaccine supports further development of Ad-based vaccines comprising additional vital components for immune therapy and AIDS vaccine development.",
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AU - Cheng, S.

AU - Kalyan, N.

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