Mucosal vaccination with a live recombinant rhinovirus followed by intradermal DNA administration elicits potent and protective HIV-specific immune responses

Abstract

Mucosal immunity is deemed crucial to control sexual transmission of human immunodeficiency virus (HIV). Herein we report the efficacy of a mucosal HIV vaccine strategy comprising intranasal (IN) vaccination with a cocktail of live recombinant human rhinoviruses (HRVs) encoding overlapping fragments of HIV Gag and full length Tat (rHRV-Gag/Tat) followed by intradermal (ID) vaccination with DNA vaccines encoding HIV Gag and Tat (pVAX-Gag-Tat). This heterologous prime-boost strategy will be referred to hereafter as rHRV-DNA. As a control, IN vaccination with wild type (wt)-HRV-A1 followed by a single ID dose of pVAX (wt-HRV-A1/pVAX vaccination) was included. rHRV-DNA vaccination elicited superior multi-functional CD8+T cell responses in lymphocytes harvested from mesenteric lymph nodes and spleens, and higher titres of Tat-specific antibodies in blood and vaginal lavages, and reduced the viral load more effectively after challenge with EcoHIV, a murine HIV challenge model, in peritoneal macrophages, splenocytes and blood compared compared with wt-HRV-A1/pVAX vaccination or administration of 3 ID doses of pVAX-Gag-Tat (3X pVAX-Gag-Tat vaccination). These data provide the first evidence that a rHRV-DNA vaccination regimen can induce HIV-specific immune responses in the gut, vaginal mucosa and systemically, and supports further testing of this regimen in the development of an effective mucosally-targeted HIV-1 vaccine.

Immunization by exposure to live virus (SIVmne/HIV-2287) during antiretroviral drug prophylaxis reduces risk of subsequent viral challenge

“…Similar to induction of antibody responses by intravaginal immunizations in the animals we studied, other studies have detected humoral and cellular immune responses after intravaginal [71,72], rectal [73,74] and nasal [75][76][77][78] administration of HIV/SIV. These observations suggest that administering prophylaxis during HIV exposures may effectively immunize individuals discordant for HIV infection, such as monogamous sexual partners and/or breastfeeding infants.…”

Oral Vaccination with a DNA Vaccine Encoding Capsid Protein of Duck Tembusu Virus Induces Protection Immunity

“…Eukaryotic expression plasmid pVAX1 has been extensively used as the backbone of the DNA vaccine and has helped virus genes express in eukaryotic cells [ 27 , 28 ]. Attenuated Salmonella typhimurium is a safe and efficient bacteria vector to carry a DNA vaccine [ 21 , 29 ].…”

Stimuli‐Responsive Biomaterials for Vaccines and Immunotherapeutic Applications

“…For instance, a recently investigated recombinant rhinovirus‐based vaccine delivered mucosally showed potent and protective HIV‐specific immune response. [ 106 ] Specifically, the vaccination elicited stronger multifunctional CD8 + T cell response and higher antibody titers. Mucosal delivery routes have long been avoided by scientists because of the many physical, chemical, and mechanical barriers that reduce the transfer of vaccine components into the blood.…”