Oral vaccination with a recombinant Salmonella vaccine vector provokes systemic HIV-1 subtype C Gag-specific CD4+ Th1 and Th2 cell immune responses in mice

Abstract

Background: Recombinant Salmonella vaccine vectors may potentially be used to induce specific CD4+ T cell responses against foreign viral antigens. Such immune responses are required features of vaccines against pathogens such as human immunodeficiency virus type 1 (HIV-1). The aim of this study was to investigate the induction of systemic HIV-1-specific CD4+ T helper (Th) responses in mice after oral immunization with a live attenuated Salmonella vaccine vector that expressed HIV-1 subtype C Gag. Groups of BALB/c mice were vaccinated orally three times (4 weeks apart) with this recombinant Salmonella. At sacrifice, 28 days after the last immunization, systemic CD4+ Th1 and Th2 cytokine responses were evaluated by enzyme-linked immunospot assay and cytometric bead array. HIV-1 Gag-specific IgG1 and IgG2a humoral responses in the serum were determined by enzyme-linked immunosorbent assay.

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

“…In an early study in a murine model, recombinant Salmonella expressing HIV Gag elicited HIV Gag-specific Th1 and Th2 type CD4 responses, as measured by production of interferon (IFN)-c/tumor necrosis factor (TNF)-a and IL-4/IL-5, respectively. 60 Env delivered by a Salmonella vector was also found to induce a predominantly CD4 T cell response, which can enhance B cell activation as well as produce anti-HIV chemokines 61 ; however, this response alone was likely an ineffective means of controlling infection as limited antiviral effector populations (CTL or antibody secreting cells) were induced. Vaccination of rhesus macaques with Salmonella expressing Env and Gag failed to confer protection, although the challenge was introduced intravenously and the mucosal response was not studied.…”

Recombinant Salmonella enterica Serovar Typhimurium as a Vaccine Vector for HIV-1 Gag

“…We successful constructed a recombinant Salmonella overexpressing codon-optimized HIV-1 Subtype C Gag in the bacterial cytoplasm [88]. When groups of BALB/c mice were orally vaccinated three times, systematic HIV-1 Gag-specific CD4 + Th1 and Th2 cytokine responses were provoked [88].…”

“…We successful constructed a recombinant Salmonella overexpressing codon-optimized HIV-1 Subtype C Gag in the bacterial cytoplasm [88]. When groups of BALB/c mice were orally vaccinated three times, systematic HIV-1 Gag-specific CD4 + Th1 and Th2 cytokine responses were provoked [88]. For Th1 responses, both HIV-1-specific interferon-gamma and tumor necrosis factor-alpha cytokines were elicited and for the Th2 responses, interleukin-4 and interleukin-5 cytokine responses were elicited [88].…”

South African HIV-1 vaccine candidates – the journey from the bench to clinical trials

“…15 Salmonella was tested as an HIV vaccine vector in mice. 18 HIV VLPs were particularly successful at boosting HIV immune responses in baboons induced by priming with either DNA vaccines 11 or BCG-based vaccines.…”