Optimized Mucosal MVA Prime/ Soluble gp120 Boost Vaccination Regimen Induces Similar Antibody Responses as an Intramuscular Regimen

Abstract

0The benefits of mucosal vaccines over injected vaccines are difficult to ascertain since mucosally 3 1 administered vaccines often induce serum antibody responses of lower magnitude than those induced by 3 2 injected vaccines. This study aimed to determine if mucosal vaccination using a modified vaccinia Ankara 3 3 expressing HIV-1 gp120 (MVA-g120) prime and HIV-1 gp120 protein boost could be optimized to induce serum 3 4 antibody responses similar to those induced by an intramuscularly (IM) administered MVA prime/gp120 boost 3 5 to allow comparison of an IM immunization regimen to a mucosal vaccination regimen for their ability to protect 3 6 against a low dose rectal SHIV challenge while inducing similar serum anti-HIV-1 antibody responses. A 3-fold 3 7higher antigen dose was required for intranasal (IN) immunization with gp120 to induce serum anti-gp120 IgG 3 8responses not significantly different than those induced by IM immunization. Gp120 fused to the Adenovirus 3 9 type 2 fiber binding domain (gp120-Ad2F), a mucosal targeting ligand, exhibited enhanced IN immunogenicity 4 0 when compared to gp120 alone. MVA-gp120 was more immunogenic after IN delivery than gastric or rectal 4 1 delivery, although serum antibodies induced by IN immunization were lower than those induced by 4 2 intramuscular immunization. Using these optimized vaccines, an IN MVA-gp120 prime, combined IM (gp120) 4 3 and IN (gp120-Ad2F) boost regimen (IN/IM+IN) induced serum anti-gp120 antibody titers similar to those 4 4 induced by the intramuscular prime/boost regimen (IM/IM) in rabbits and non-human primates. Despite the 4 5 induction of similar systemic anti-HIV-1 antibody responses, neither the IM/IM nor the IN/IM+IN regimen 4 6 induced elevated anti-HIV-1 mucosal IgA responses nor protected against a repeated low-dose rectal SHIV 4 7 challenge. These results demonstrate that immunization regimens utilizing the IN route are able to induce 4 8 serum antigen-specific antibody responses similar to those induced by systemic immunization 4 9

Optimized Mucosal Modified Vaccinia Virus Ankara Prime/Soluble gp120 Boost HIV Vaccination Regimen Induces Antibody Responses Similar to Those of an Intramuscular Regimen

“…(This article was submitted to an online preprint archive [43].) vaccines (45,46), and our previous success using MF59 (a squalene-based adjuvant) in a prime/boost vaccine regimen led to our use of AddaVax in the current study (8).…”