Combination nanovaccine enhances influenza vaccine efficacy in aged animals

Abstract

Event Abstract Back to Event Combination nanovaccine enhances influenza vaccine efficacy in aged animals Kathleen Ross1, Jonathan Goodman1, Matthew Jefferson2, Hyelee Loyd3, Metin Uz1, Michael Wannemuehler4, Surya Mallapragada1, Susan Carpenter3, Marian Kohut5 and Balaji Narasimhan1 1 Iowa State University, Chemical & Biological Engineering, United States 2 Iowa State University, Neuroscience, United States 3 Iowa State University, Animal Science, United States 4 Iowa State University, Veterinary Microbiology & Preventive Medicine, United States 5 Iowa State University, Kinesiology, United States Elderly populations have suboptimal responses to influenza vaccination due to age-associated deficiencies in immune responses[1],[2]. Due to poor antibody responses, measures of cell-mediated immunity may better predict protection in aged individuals[1]. Thus, influenza vaccines that stimulate both antibody and cell-mediated immunity would benefit aged populations. Polyanhydride nanoparticles are capable of both adjuvanting and sustaining the release of influenza antigens[3],[4]. Pentablock copolymer hydrogels form depots of antigen and/or nanoparticles that promote rapid development of antibody titers[5]. In this work, the ability of a combination nanovaccine composed of nanoparticles and hydrogels to enhance neutralizing antibody titers and cell-mediated immunity was studied in aged mice. Aged (17 mo.) and young (2 mo.) mice were immunized thrice (days 0, 21, and 56) with 10 µg of H5 hemagglutinin trimer (sH53), or a combination nanovaccine (2 µg H53 encapsulated into 200 µg nanoparticles + 8 µg H53 entrapped in 25 mg hydrogel). Serum samples were collected at 35, 56, and 66 days post-immunization and the neutralizing antibody titer was determined. To assess T cell induction, both mice received 100 µg of ovalbumin (OVA) either solubly or within the combination nanovaccine at day 66. After 6 days, draining lymph nodes were collected and homogenized. Cells were stimulated with PMA/ionomycin and subsequently labelled with anti-CD8β, anti-CD4, anti-IFNγ, and anti-TNFα. In young mice, robust neutralizing antibody titers were detected at each time point. In contrast, no titers were detected in aged mice receiving either the sH53 or the combination nanovaccine until after administration of a 3rd dose. However, the average titer in mice receiving the combination nanovaccine was five-fold higher than that in the sH53-immunized mice. The combination nanovaccine induced greater numbers of CD4+ and CD8+ T cells in draining lymph nodes when compared to that induced by soluble OVA in both age groups; however, this effect was only statistically significant in young mice. Additionally, the aged mice had greater numbers of CD4+ and CD8+ cells producing IFNγ and TNFα in comparison to young mice (Fig. 1). Fig. 1. Combination nanovaccine immunization enhanced T cell response in aged mice. Mice administered the combination nanovaccine demonstrated greater numbers of CD8+ IFNγ+ TNFα+ T cells than mice administered soluble antigen in both age groups. In this work, a combination nanovaccine was demonstrated to enhance both antibody- and cell-mediated immunity in aged mice. While the neutralizing antibody responses in aged mice were impaired, the combination nanovaccine induced enhanced titers in comparison to that induced by sH53. In addition, the combination nanovaccine induced greater numbers of functional T cells after immunization in both age groups. These data indicate the potential of the combination nanovaccine to increase vaccine efficacy in aged populations.