Multiple low-dose challenges in a Rhesus Macaque AIDS vaccine trial result in an evolving host response that affects protective outcome

Christian Selinger, Natasa Strbo, Louis Gonzalez, Lauri Aicher, Jeffrey M. Weiss, G. Lynn Law, Robert E. Palermo, Monica Vaccari, Genoveffa Franchini, Eckhard R. Podack, Michael G. Katze

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Using whole-blood transcriptional profiling, we investigated differences in the host response to vaccination and challenge in a rhesus macaque AIDS vaccine trial. Samples were collected from animals prior to and after vaccination with live, irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-Ig loaded with simian immunodeficiency virus (SIV) peptides, either alone or in combination with a SIV-gp120 protein boost. Additional samples were collected following multiple low-dose rectal challenges with SIVmac251. Animals in the boosted group had a 73% reduced risk of infection. Surprisingly, few changes in gene expression were observed during the vaccination phase. Focusing on postchallenge comparisons, in particular for protected animals, we identified a host response signature of protection comprised of strong interferon signaling after the first challenge, which then largely abated after further challenges. We also identified a host response signature, comprised of early macrophage-mediated inflammatory responses, in animals with undetectable viral loads 5 days after the first challenge but with unusually high viral titers after subsequent challenges. Statistical analysis showed that prime-boost vaccination significantly lowered the probability of infection in a time-consistent manner throughout several challenges. Given that humoral responses in the prime-boost group were highly significant prechallenge correlates of protection, the strong innate signaling after the first challenge suggests that interferon signaling may enhance vaccine-induced antibody responses and is an important contributor to protection from infection during repeated low-dose exposure to SIV.

Original languageEnglish (US)
Pages (from-to)1650-1660
Number of pages11
JournalClinical and Vaccine Immunology
Volume21
Issue number12
DOIs
StatePublished - Dec 1 2014

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

Cite this

Selinger, C., Strbo, N., Gonzalez, L., Aicher, L., Weiss, J. M., Law, G. L., Palermo, R. E., Vaccari, M., Franchini, G., Podack, E. R., & Katze, M. G. (2014). Multiple low-dose challenges in a Rhesus Macaque AIDS vaccine trial result in an evolving host response that affects protective outcome. Clinical and Vaccine Immunology, 21(12), 1650-1660. https://doi.org/10.1128/CVI.00455-14