Oral Immunization with a Recombinant Lactococcus lactis–Expressing HIV-1 Antigen on Group A Streptococcus Pilus Induces Strong Mucosal Immunity in the Gut

Abstract

The induction of a potent humoral and cellular immune response in mucosal tissue is important for the development of an effective HIV vaccine. Most of the current HIV vaccines under development use the intramuscular route for immunization, which is relatively poor in generating potent and long-lived mucosal immune responses. Here, we explore the ability of an oral vaccination with a probiotic organism, Lactococcus lactis (L. lactis), to elicit HIV-specific immune responses in the mucosal and systemic compartments of BALB/c mice. We expressed the HIV-1 Gag-p24 on the tip of the T3 pilus of Streptococcus pyogenes as a fusion to the Cpa protein (LL-Gag). Following four monthly LL-Gag oral immunizations we observed strong Gag-specific IgG and IgA responses in serum, feces, and vaginal secretions. However, the Gag-specific CD8 T cell responses in the blood were at or below our detection limit. Following an intramuscular modified vaccinia Ankara (MVA)/Gag boost, we observed a robust Gag-specific CD8 T cell responses both in systemic and mucosal tissue, including intraepithelial and lamina propria lymphocytes of the small intestine, Peyer's patches, and mesenteric lymph nodes. Consistent with strong immunogenicity, the LL-Gag induced activation of CD11c+ CD11b+ dendritic cells in the Peyer's patches after oral immunization. Our results demonstrate that oral immunization with L. lactis expressing an antigen on the tip of the Group-A streptococcus pilus serves as an excellent vaccine platform to induce strong mucosal humoral and cellular immunity against HIV.

Vaccination against Salmonella Infection: the Mucosal Way

“…In the context of S. Typhi Omps, encapsulation in PLGA beads increases specific B cell responses in PPs and MLNs of orally immunized mice compared to Omps alone, suggesting the versatility of this delivery system (222). Outside chemically based delivery systems, viral and bacterial Ags expressed in safe natural carriers such as probiotic strains generate specific local and systemic protective immunity observed in case of S. Typhimurium infection in mice when fed orally (223)(224)(225)(226). Another manner to contribute to the good delivery of Ags in the intestinal mucosa would consist of orally coadministering the vaccine formulation with the protease inhibitor U-Omp19 from Brucella, which has been shown both to increase the half-life of Ags delivered along the GI tract and to activate APCs (227).…”

Modified Vaccinia Ankara Based SARS-CoV-2 Vaccine Expressing Full-Length Spike Induces Strong Neutralizing Antibody Response

“…These were performed as described previously (27). Briefly, Nunc high-binding ELISA plates (Thermo Fisher Scientific; Waltham, MA, USA) were coated with 2 µg/ml of recombinant SARS-CoV-2 proteins (S1 and RBD-His proteins were produced in the lab and S1 + S2 ECD spike protein was purchased from Sino Biologicals) in Dulbecco's phosphate-buffered saline (DPBS) and incubated overnight at 4 °C.…”

Coinfections and comorbidities in African health systems: At the interface of infectious and noninfectious diseases

“…Experimental studies have shown that intranasal probiotics of Lactobacillus strains stimulate immune responses in the respiratory tract, offering protection from viral (H1N1) infection [ 107 , 108 ]. Probiotics have been used to deliver antigens or adjuvants directly to the “unfriendly” gastrointestinal tract in HIV vaccine development [ 109 ] and as a potential cryopreservative and immunomodulator of mucosal immune response in Hepatitis B vaccines [ 110 ]. Despite existing evidence on the role of probiotics to enhance vaccine-specific immunity, there is a need for rigorous longitudinal mechanistic and efficacy studies in paediatrics for different vaccines.…”