A simultaneous oral and intramuscular prime/sublingual boost with a DNA/Modified Vaccinia Ankara viral vector-based vaccine induces simian immunodeficiency virus-specific systemic and mucosal immune responses in juvenile rhesus macaques

• Type of Material: Article
• Authors: Alan D. Curtis, University of North Carolina; Kara Jensen, University of North Carolina; Koen K.A. Van Rompay, University of California Davis; Rama Amara, Emory University; Pamela A. Kozlowski, Louisiana State University; Dr. Kristina De Paris, University of North Carolina
• Language: English
• Date: 2018-10-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
• Final Published Version (URL): http://dx.doi.org/10.1111/jmp.12372
• Title of Journal or Parent Work: Journal of Medical Primatology
• ISSN: 0047-2565
• Volume: 47
• Issue: 5
• Start Page: 288
• End Page: 297
• Grant/Funding Information: Research reported in this publication was supported by the Center for AIDS Research award number P30AI050410.; This work was supported by the National Institutes of Health (R01DE022287) to KDP and by the Office of Research Infrastructure Programs/OD (P51OD011107) to CNPRC.; The UNC Flow Cytometry Core Facility is supported in part by P30 CA016086 Cancer Center Core Support Grant to the UNC Lineberger Comprehensive Cancer Center and in part by the North Carolina Biotech Center Institutional Support Grant 2017‐IDG‐1025 and by the National Institutes of Health 1UM2AI30836‐01.
• Keywords: Science & Technology; Veterinary Sciences; IMMUNIZATION; HELPER TFH CELLS; PROTECTION; INFANT; CHALLENGE; HIV; T-CELLS; oral route; INFECTION; ADJUVANT; IMMUNOGENICITY; Zoology; SIV; pediatric vaccine; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Immunology; Health Sciences, Public Health

Abstract

Background: A pediatric vaccine to prevent breast milk transmission of human immunodeficiency virus (HIV) may generate greater immune responses at viral entry sites if given by an oral route. Methods: We compared immune responses induced in juvenile macaques by prime/boosting with simian immunodeficiency virus (SIV)-expressing DNA/modified vaccinia Ankara virus (MVA) by the intramuscular route (IM), the oral (O)/tonsillar routes (T), the O/sublingual (SL) routes, and O+IM/SL routes. Results: O/T or O/SL immunization generated SIV-specific T cells in mucosal tissues but failed to induce SIV-specific IgA in saliva or stool or IgG in plasma. IM/IM or O+IM/SL generated humoral and cellular responses to SIV. IM/IM generated greater frequencies of TFH in spleen, but O+IM/SL animals had higher avidity plasma IgG and more often demonstrated mucosal IgA responses. Conclusion: These results suggest that codelivery of HIV DNA/MVA vaccines by the oral and IM routes might be optimal for generating both systemic and mucosal antibodies.