Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Abstract

CD4+ T cells in the mucosa of the gastrointestinal (GI) tract are preferentially targeted and depleted by HIV. As such, the induction of an effective anti-HIV immune response in the mucosa of the GI tract-through vaccination-could protect this vulnerable population of cells. Mucosal vaccination provides a promising means of inducing robust humoral and cellular responses in the GI tract. Here we review data from the literature about the effectiveness of various mucosal vaccination routes-oral (intraintestinal/tonsilar/sublingual), intranasal, and intrarectal-with regard to the induction of immune responses mediated by cytotoxic T cells and antibodies in the GI mucosa, as well as protective efficacy in challenge models. We present data from the literature indicating that mucosal routes have the potential to effectively elicit GI mucosal immunity and protect against challenge. Given their capacity for the induction of anti-HIV immune responses in the GI mucosa, we propose that mucosal routes, including the nonconventional sublingual, tonsilar, and intrarectal routes, be considered for the delivery of the next generation HIV vaccines. However, further studies are necessary to determine the ideal vectors and vaccination regimens for these routes of immunization and to validate their efficacy in controlling HIV infection. HIV Epidemics and Treatment HIV infection has resulted in the death of millions since the early 1980s, and has been responsible for significant morbidity and decline in quality of life for millions more. Each year, an estimated 50,000 people are newly infected with the virus in the United States alone, adding to the 34 million currently living with the virus worldwide.

Recombinant-attenuated Salmonella Pullorum strain expressing the hemagglutinin-neuraminidase protein of Newcastle disease virus (NDV) protects chickens against NDV and Salmonella Pullorum challenge

“…The sIgA antibody is the first line of defense against microbial infection, and it is the primary antibody mediating mucosal immunity [ 14 15 ]. The mucosal immune effect of oral inoculations can be assessed by examining sIgA antibody levels, as well as by examining systemic antibodies and cell-mediated immune responses [ 12 29 ]. Compared to the control group, the HI antibody titer, the intestinal sIgA levels of both C79-13Δ crp Δ asd (pYA-HN) strains and the NDV live vaccine-immunized groups all showed significant increases at the second week after immunization.…”

Oral immunization of a non-recombinant Lactococcus lactis surface displaying influenza hemagglutinin 1 (HA1) induces mucosal immunity in mice

“…This vaccine is administered intramuscularly and therefore, induces immune response similar to IIV [ 7 ]. However, a few serious adverse events associated with this vaccine such as vasovagal syncope, pericardial effusion and Bell’s palsy were previously reported [ 8 ]. Taken together, influenza vaccines that are currently available present several drawbacks, including their limited ability at stimulating mucosal immunity without compromising safety issues.…”

E2 multimeric scaffold for vaccine formulation: immune response by intranasal delivery and transcriptome profile of E2-pulsed dendritic cells

“…A shared feature of many pathogens is that the infection occurs or initiates at a mucosal surface. While systemic vaccination offers protection against pathogens such as polio and influenza viruses, induction of mucosal immunity is required for effective protection against pathogens such as HIV, human papillomavirus, herpes viruses, Vibrio cholera and the Mycobacterium species [ 8 – 13 ]. Antibodies patrolling the mucosal epithelium appear to play a crucial role in blocking HIV-1 mucosal challenge [ 14 ].…”