RT Journal Article
SR Electronic
T1 Optimized Mucosal MVA Prime/ Soluble gp120 Boost Vaccination Regimen Induces Similar Antibody Responses as an Intramuscular Regimen
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 573394
DO 10.1101/573394
A1 Dorothy I. Jones
A1 Justin J. Pollara
A1 Brandi T. Johnson-Weaver
A1 Celia C. LaBranche
A1 David C. Montefiori
A1 David J. Pickup
A1 Sallie R. Permar
A1 Soman N. Abraham
A1 Massimo Maddaloni
A1 David W. Pascual
A1 Herman F. Staats
YR 2019
UL http://biorxiv.org/content/early/2019/03/11/573394.abstract
AB The benefits of mucosal vaccines over injected vaccines are difficult to ascertain since mucosally administered vaccines often induce serum antibody responses of lower magnitude than those induced by injected vaccines. This study aimed to determine if mucosal vaccination using a modified vaccinia Ankara expressing HIV-1 gp120 (MVA-g120) prime and HIV-1 gp120 protein boost could be optimized to induce serum antibody responses similar to those induced by an intramuscularly (IM) administered MVA prime/gp120 boost to allow comparison of an IM immunization regimen to a mucosal vaccination regimen for their ability to protect against a low dose rectal SHIV challenge while inducing similar serum anti-HIV-1 antibody responses. A 3-fold higher antigen dose was required for intranasal (IN) immunization with gp120 to induce serum anti-gp120 IgG responses not significantly different than those induced by IM immunization. Gp120 fused to the Adenovirus type 2 fiber binding domain (gp120-Ad2F), a mucosal targeting ligand, exhibited enhanced IN immunogenicity when compared to gp120 alone. MVA-gp120 was more immunogenic after IN delivery than gastric or rectal delivery, although serum antibodies induced by IN immunization were lower than those induced by intramuscular immunization. Using these optimized vaccines, an IN MVA-gp120 prime, combined IM (gp120) and IN (gp120-Ad2F) boost regimen (IN/IM+IN) induced serum anti-gp120 antibody titers similar to those induced by the intramuscular prime/boost regimen (IM/IM) in rabbits and non-human primates. Despite the induction of similar systemic anti-HIV-1 antibody responses, neither the IM/IM nor the IN/IM+IN regimen induced elevated anti-HIV-1 mucosal IgA responses nor protected against a repeated low-dose rectal SHIV challenge. These results demonstrate that immunization regimens utilizing the IN route are able to induce serum antigen-specific antibody responses similar to those induced by systemic immunizationIMPORTANCE Mucosal vaccination is proposed as a method of immunization able to induce protection against mucosal pathogens that is superior to protection provided by parenteral immunization. However, mucosal vaccination often induces serum antigen-specific immune responses of lower magnitude than those induced by parenteral immunization, making the comparison of mucosal and parenteral immunization difficult. We identified vaccine parameters that allowed an immunization regimen consisting of an IN prime followed with boosters administered by both IN and IM routes to induce serum antibody responses similar to those induced by IM prime/boost vaccination. Additional studies are needed to determine the potential benefit of mucosal immunization for HIV-1 and other mucosally-transmitted pathogens.