Immunization with adenovirus at the large intestinal mucosa as an effective vaccination strategy against sexually transmitted viral infection

Abstract

The large intestinal mucosa contains immunological structures that may potentially serve as a site for induction of mucosal immunity against infections. Adenovirus (Ad), which is effective in gene transfer to epithelia, may be an ideal antigen delivery system for vaccination at the large intestinal mucosa. To investigate this potential, we immunized mice with recombinant replication-deficient Ad through a single intracolorectal (ICR) administration. Effective transfer of encoded genes was found in both the epithelial layer and lamina propria of the colorectal mucosa. Dendritic cells were able to transfer antigen to the draining lymph nodes, where antigen-specific CD8(+) T cells were primed. Functional antigen-specific CD8(+) T cells and IgA-specific antibodies were detected during the effector phase in the large intestine. Compared to other immunization routes (intranasal, subcutaneous), ICR immunization induced stronger colorectal immune responses and more potent protection against rectal challenge with pathogenic viruses. Further, this immunization strategy provided vaginal protection, more potent than that induced by vaccination in the nose or skin. Therefore, large intestine mucosal immunization using Ad represents an effective vaccination strategy against virus infection at both rectal and vaginal mucosal tissue sites.

Route of Adenovirus-Based HIV-1 Vaccine Delivery Impacts the Phenotype and Trafficking of Vaccine-Elicited CD8 + T Lymphocytes

“…However, our findings contrast with those of other studies that have suggested that mucosal rAd vector routing is advantageous for inducing CD8 ϩ T-lymphocyte responses at mucosal surfaces (14,16,27,32,36,43,46). We suspect that these differences may be related to the specifics of the various experimental systems utilized, such as differences in immunization techniques or vector doses.…”

“…1A), whereas previous studies have shown that higher volumes of intranasal instillation mediate passage of the instillate to the lower respiratory tract (39). Some studies have also surgically or chemically manipulated mucosal surfaces (44,46), which could lead to persistent inflammation at the site of antigen delivery and alter the dynamics of antigen uptake and presen- Using adoptive transfer studies, we assessed the initial priming and trafficking patterns of antigen-specific CD8 ϩ T lymphocytes following immunization. I.m.…”

IL-15 Expands Unconventional CD8ααNK1.1+ T Cells but Not Vα14Jα18+ NKT Cells

“…Small intestine was removed from mice and fragmented into small pieces and stirred for 30 min at 37°C with Ca 2ϩ -and Mg 2ϩ -free HBSS containing 10% FBS, 15 mM HEPES, 5 mM EDTA, 0.014% w/v DTT, and 100 g ml Ϫ1 gentamicin to isolate epithelial cells and IELs (10). IELs were purified from the cell suspension by a 40/67% gradient of Percoll (Sigma-Aldrich).…”

Intravaginal immunization with HPV vectors induces tissue-resident CD8+ T cell responses

“…Most replication-defective viral vectors for genetic vaccination have been administered systemically and have successfully induced CD8 + T cell responses, but few of these vectors have been used for mucosal vaccination (31,32). HPV pseudoviruses (PsV), composed of the viral L1 and L2 proteins and a double-stranded DNA pseudogenome, have several attractive features as vectors for genetic immunization of the female genital mucosa, which is the natural target tissue for many HPV types.…”