Assessing the In Vivo Effectiveness of Cationic Lipid Nanoparticleswith a Triple Adjuvant for Intranasal Vaccination against theRespiratory Pathogen Bordetella pertussis

Aibani, N; Patel, P; Buchanan, R; Strom, S; Wasan, KM; Hancock, REW; Gerdts, V; Wasan, EK

Abstract

Continuous outbreaks of pertussis around the worldsuggest inadequate immune protection in infants and weakenedimmune responses induced over time by the acellular pertussisvaccine. Vaccine adjuvants provide a means to improve vaccineimmunogenicity and support long-term adaptive immunity againstpertussis. An acellular pertussis vaccine was prepared withpertactin, pertussis toxin, andfimbriae 2/3 antigens combinedwith a triple-adjuvant system consisting of innate defense regulatorpeptide IDR 1002, a Toll-like receptor-3 agonist poly(I:C), and apolyphosphazene in afixed combination. The vaccine wasdelivered intranasally in a cationic lipid nanoparticle formulationfabricated by simple admixture and two schema for addition of antigens (LT-A, antigens associated outside of L-TriAdj, and LAT,antigens associated inside of L-TriAdj) to optimize particle size and cationic surface charge. In the former, antigens were associatedwith the lipidic formulation of the triple adjuvant by electrostatic attraction. In the latter, the antigens resided in the interior of thelipid nanoparticle. Two dose levels of antigens were used with adjuvant comprised of the triple adjuvant with or without the lipidnanoparticle carrier. Formulation of vaccines with the triple adjuvant stimulated systemic and mucosal immune responses. The lipidnanoparticle vaccines favored a Th1 type of response with higher IgG2a and IgA serum antibody titers particularly for pertussis toxinand pertactin formulated at the 5 mu g dose level in the admixed formulation. Additionally, the lipid nanoparticle vaccines resulted inhigh nasal SIgA antibodies and an early (4 weeks post vaccination) response after a single vaccination dose. The LT-A nanoparticlestrended toward higher titers of serum antibodies compared to LAT. The cationic lipid-based vaccine nanoparticles formulated with atriple adjuvant showed encouraging results as a potential formulation for intranasally administered pertussis vaccines

Keywords: pertussis; triple adjuvant; cationic lipids; nanoparticles; intranasal; mucosal immunity

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