Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen

Mauricio A Arias,Andrew Loxley,Christy Eatmon,Griet Van Roey,David Fairhurst,Mark Mitchnick,Philip Dash,Tom Cole,Frank Wegmann,Quentin Sattentau,Robin Shattock

doi:10.1016/j.vaccine.2010.11.084

Abstract

Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates.

Highlights

The HIV pandemic continues to be a major global health priority, and while there has been good progress in the development of antiretroviral drugs that have contributed to longer survival of infected individuals, prospects of an effective vaccine against HIV remain largely elusive [1;2]
Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates
We have developed NP made of yellow carnauba (YC) wax with high colloidal stability, low cost and scalable manufacture that would provide a rapid product development pathway

Summary

Introduction

The HIV pandemic continues to be a major global health priority, and while there has been good progress in the development of antiretroviral drugs that have contributed to longer survival of infected individuals, prospects of an effective vaccine against HIV remain largely elusive [1;2]. A critical goal of HIV vaccination is the induction of mucosal humoral immune responses. This is predicated on the production of antibodies (Ab) with capacity of hindering the entrance of HIV and its subsequent interaction with target cells at mucosal sites either by viral neutralization, aggregation, or Fc receptor mediated mechanisms [7]. Because HIV antigens (Ag) alone induce very low if any immune responses, the use of adjuvants is of paramount importance. Compounds or macromolecular complexes that boost the potency and longevity of specific immune responses to Ag with little toxicity and long-lasting immune effects [8]. NP may increase Ag presentation capacity, boosting cellular and humoral immune responses

Methods

Results

Conclusion