This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We previously showed that immunization of pig-tailed macaques with the N7 Env, which had a N-linked glycan at amino acid residue 197 removed, resulted in enhanced neutralizing antibody (NAb) response not only against the homologous virus, 89.6, but also HIV-1 SF162 and a standard panel of subtype B primary isolates. In this study, we aimed to extend these studies to evaluate the protective efficacy of N7 Env vaccines against a heterologous CCR5 virus challenge. We immunized three groups of pig-tailed macaques (N=6/group) with a """"""""prime-boost"""""""" regimen, consisting of priming with recombinant vaccinia virus and boosting with recombinant proteins. Two of these groups were immunized with either wild-type or mutant N7 Env vaccines. An additional group of animals received both N7 Env and SIV Gag-Pol vaccines. Control animals received parental vaccinia virus and adjuvant only. All animals generated lentivirus-specific antibody responses, including NAb against the heterologous virus SF162, albeit at 5- to10-fold less than what we observed in the first study described above. This prompted us to administer an additional booster immunization. However, no increase in NAb titer was observed, consistent with the notion that the magnitude of response was determined largely by the effectiveness of the primary immunization. After challenge with an intrarectal inoculation of SHIV162P4, all control and immunized animals were infected, consistent with the low titer of Nab titer at the day of challenge. However, animals immunized with the N7 Env showed significant reduction of peak viral load and those received both N7 Env and SIV Gag-Pol vaccines showed reduction of setpoint viral loads. These results indicate that protective immunity against a heterologous virus can be generated by the prime boost immunization regimen. This experiment was concluded in July, 2010 and the remaining animals transferred to Colony Health for follow up studies.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000166-50
Application #
8357597
Study Section
Special Emphasis Panel (ZRR1-CM-8 (02))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
50
Fiscal Year
2011
Total Cost
$377,899
Indirect Cost
Name
University of Washington
Department
Veterinary Sciences
Type
Other Domestic Higher Education
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
McAdams, Ryan M; McPherson, Ronald J; Kapur, Raj P et al. (2017) Focal Brain Injury Associated with a Model of Severe Hypoxic-Ischemic Encephalopathy in Nonhuman Primates. Dev Neurosci 39:107-123
Klegarth, Amy R; Ezeonwu, Chigozie A; Rompis, Aida et al. (2017) Survey of Treponemal Infections in Free-Ranging and Captive Macaques, 1999-2012. Emerg Infect Dis 23:816-819
Hallum, Luke E; Shooner, Christopher; Kumbhani, Romesh D et al. (2017) Altered Balance of Receptive Field Excitation and Suppression in Visual Cortex of Amblyopic Macaque Monkeys. J Neurosci 37:8216-8226
Seeman, Stephanie C; Mogen, Brian J; Fetz, Eberhard E et al. (2017) Paired Stimulation for Spike-Timing-Dependent Plasticity in Primate Sensorimotor Cortex. J Neurosci 37:1935-1949
Balakrishnan, Ashwini; Goodpaster, Tracy; Randolph-Habecker, Julie et al. (2017) Analysis of ROR1 Protein Expression in Human Cancer and Normal Tissues. Clin Cancer Res 23:3061-3071
Shooner, Christopher; Hallum, Luke E; Kumbhani, Romesh D et al. (2017) Asymmetric Dichoptic Masking in Visual Cortex of Amblyopic Macaque Monkeys. J Neurosci 37:8734-8741
Rembado, Irene; Zanos, Stavros; Fetz, Eberhard E (2017) Cycle-Triggered Cortical Stimulation during Slow Wave Sleep Facilitates Learning a BMI Task: A Case Report in a Non-Human Primate. Front Behav Neurosci 11:59
Richter, Maximilian; Yumul, Roma; Saydaminova, Kamola et al. (2016) Preclinical safety, pharmacokinetics, pharmacodynamics, and biodistribution studies with Ad35K++ protein: a novel rituximab cotherapeutic. Mol Ther Methods Clin Dev 5:16013
McLoon, Linda K; Christiansen, Stephen P; Ghose, Geoffrey M et al. (2016) Improvement of Eye Alignment in Adult Strabismic Monkeys by Sustained IGF-1 Treatment. Invest Ophthalmol Vis Sci 57:6070-6078
Liao, Hsi-Wen; Ren, Xiaozhi; Peterson, Beth B et al. (2016) Melanopsin-expressing ganglion cells on macaque and human retinas form two morphologically distinct populations. J Comp Neurol 524:2845-72

Showing the most recent 10 out of 311 publications