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Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs.

Publication ,  Journal Article
Francica, JR; Zak, DE; Linde, C; Siena, E; Johnson, C; Juraska, M; Yates, NL; Gunn, B; De Gregorio, E; Flynn, BJ; Valiante, NM; Malyala, P ...
Published in: Blood Adv
November 28, 2017

Adjuvants have a critical role for improving vaccine efficacy against many pathogens, including HIV. Here, using transcriptional RNA profiling and systems serology, we assessed how distinct innate pathways altered HIV-specific antibody responses in nonhuman primates (NHPs) using 8 clinically based adjuvants. NHPs were immunized with a glycoprotein 140 HIV envelope protein (Env) and insoluble aluminum salts (alum), MF59, or adjuvant nanoemulsion (ANE) coformulated with or without Toll-like receptor 4 (TLR4) and 7 agonists. These were compared with Env administered with polyinosinic-polycytidylic acid:poly-L-lysine, carboxymethylcellulose (pIC:LC) or immune-stimulating complexes. Addition of the TLR4 agonist to alum enhanced upregulation of a set of inflammatory genes, whereas the TLR7 agonist suppressed expression of alum-responsive inflammatory genes and enhanced upregulation of antiviral and interferon (IFN) genes. Moreover, coformulation of the TLR4 or 7 agonists with alum boosted Env-binding titers approximately threefold to 10-fold compared with alum alone, but remarkably did not alter gene expression or enhance antibody titers when formulated with ANE. The hierarchy of adjuvant potency was established after the second of 4 immunizations. In terms of antibody durability, antibody titers decreased ∼10-fold after the final immunization and then remained stable after 65 weeks for all adjuvants. Last, Env-specific Fc-domain glycan structures and a series of antibody effector functions were assessed by systems serology. Antiviral/IFN gene signatures correlated with Fc-receptor binding across all adjuvant groups. This study defines the potency and durability of 8 different clinically based adjuvants in NHPs and shows how specific innate pathways can alter qualitative aspects of Env antibody function.

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Published In

Blood Adv

DOI

ISSN

2473-9529

Publication Date

November 28, 2017

Volume

1

Issue

25

Start / End Page

2329 / 2342

Location

United States

Related Subject Headings

  • 3201 Cardiovascular medicine and haematology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Francica, J. R., Zak, D. E., Linde, C., Siena, E., Johnson, C., Juraska, M., … Seder, R. A. (2017). Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs. Blood Adv, 1(25), 2329–2342. https://doi.org/10.1182/bloodadvances.2017011411
Francica, Joseph R., Daniel E. Zak, Caitlyn Linde, Emilio Siena, Carrie Johnson, Michal Juraska, Nicole L. Yates, et al. “Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs.Blood Adv 1, no. 25 (November 28, 2017): 2329–42. https://doi.org/10.1182/bloodadvances.2017011411.
Francica JR, Zak DE, Linde C, Siena E, Johnson C, Juraska M, et al. Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs. Blood Adv. 2017 Nov 28;1(25):2329–42.
Francica, Joseph R., et al. “Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs.Blood Adv, vol. 1, no. 25, Nov. 2017, pp. 2329–42. Pubmed, doi:10.1182/bloodadvances.2017011411.
Francica JR, Zak DE, Linde C, Siena E, Johnson C, Juraska M, Yates NL, Gunn B, De Gregorio E, Flynn BJ, Valiante NM, Malyala P, Barnett SW, Sarkar P, Singh M, Jain S, Ackerman M, Alam M, Ferrari G, Salazar A, Tomaras GD, O’Hagan DT, Aderem A, Alter G, Seder RA. Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs. Blood Adv. 2017 Nov 28;1(25):2329–2342.

Published In

Blood Adv

DOI

ISSN

2473-9529

Publication Date

November 28, 2017

Volume

1

Issue

25

Start / End Page

2329 / 2342

Location

United States

Related Subject Headings

  • 3201 Cardiovascular medicine and haematology