Dendritic cell targeted HIV‐1 gag protein vaccine provides help to a recombinant Newcastle disease virus vectored vaccine including mobilization of protective CD8⁺ T cells

Abstract

IntroductionRecombinant Newcastle Disease virus (rNDV) vectored vaccines are safe mucosal applicable vaccines with intrinsic immune‐modulatory properties for the induction of efficient immunity. Like all viral vectored vaccines repeated inoculation via mucosal routes invariably results to immunity against viral vaccine vectors. To obviate immunity against viral vaccine vectors and improve the ability of rNDV vectored vaccines in inducing T cell immunity in murine air way we have directed dendritic cell targeted HIV‐1 gag protein (DEC‐Gag) vaccine; for the induction of helper CD4+ T cells to a Recombinant Newcastle disease virus expressing codon optimized HIV‐1 Gag P55 (rNDV‐L‐Gag) vaccine.MethodsWe do so through successive administration of anti‐DEC205‐gagP24 protein plus polyICLC (DEC‐Gag) vaccine and rNDV‐L‐Gag. First strong gag specific helper CD4+ T cells are induced in mice by selected targeting of anti‐DEC205‐gagP24 protein vaccine to dendritic cells (DC) in situ together with polyICLC as adjuvant. This targeting helped T cell immunity develop to a subsequent rNDV‐L‐Gag vaccine and improved both systemic and mucosal gag specific immunity.ResultsThis sequential DEC‐Gag vaccine prime followed by an rNDV‐L‐gag boost results to improved viral vectored immunization in murine airway, including mobilization of protective CD8+ T cells to a pathogenic virus infection site.ConclusionThus, complementary prime boost vaccination, in which prime and boost favor distinct types of T cell immunity, improves viral vectored immunization, including mobilization of protective CD8+T cells to a pathogenic virus infection site such as the murine airway.

Harnessing CD8+ T Cells Under HIV Antiretroviral Therapy

“…CD8 + T cell vaccine therapies against HIV aim to stimulate pre-existing and/or generate de novo HIV-specific CD8 + T cell responses to suppress viral replication through the clearance of HIV-infected cells. To date, therapeutic vaccine regimens, which range from recombinant DNA and viral vectors to dendritic cell vaccines (195, 196), have only shown a modest effect, and a minimal delay in virus rebound following ATI, which may be due to limited immunogenicity of the vaccine [reviewed in (197)]. The limited efficacy of current therapeutic vaccines may also be due to HIV escape or lack of restoration of CD8 + T cell function.…”

Induction of Immune Response in Animal Model Using Recombinant Anti-NDV Vaccine

“…Although the traditional inactivated vaccines against ND are effective in protecting the animal, there are major disadvantages in using this vaccine that makes the development of alternative methods necessary (9). In recent years, there have been extended efforts to develop new subunit vaccines against ND and other avian diseases (6, 7, 10, 11). Ge et al .…”

Recombinant antigen delivery to dendritic cells as a way to improve vaccine design

“…Immunization of mice with two doses of scDEC-gag p24 in the presence of Poly ICLC was able to induce protection after an intranasal challenge with a vaccinia virus expressing the gag protein. 53 This type of strategy is also very promising because it is easier to scale up for mass administration, since a single-chain antibody is easier to produce than a whole antibody containing two chains. Antigen delivery to the DEC205 receptor was also used in an attempt to increase the immunogenicity of DNA vaccines.…”