Immunogenicity of an adjuvanted broadly active influenza vaccine in immunocompromised and diverse populations

IF 6.1 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Dylan A. Hendy, Erik S. Pena, Luis Ontiveros-Padilla, Timothy A. Dixon, Denzel D. Middleton, Grace L. Williamson, Nicole Rose Lukesh, Sean R. Simpson, Rebeca T. Stiepel, Md Jahirul Islam, Michael A. Carlock, Ted M. Ross, Eric M. Bachelder, Kristy M. Ainslie
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引用次数: 0

Abstract

Influenza virus outbreaks are a major burden worldwide each year. Current vaccination strategies are inadequate due to antigenic drift/shift of the virus and the elicitation of low immune responses. The use of computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) immunogens subvert the constantly mutating viruses; however, they are poorly immunogenic on their own. To increase the immunogenicity of subunit vaccines such as this, adjuvants can be delivered with the vaccine. For example, agonists of the stimulator of interferon genes (STING) have proven efficacy as vaccine adjuvants. However, their use in high-risk populations most vulnerable to influenza virus infection has not been closely examined. Here, we utilize a vaccine platform consisting of acetalated dextran microparticles loaded with COBRA HA and the STING agonist cyclic GMP-AMP. We examine the immunogenicity of this platform in mouse models of obesity, aging, and chemotherapy-induced immunosuppression. Further, we examine vaccine efficacy in collaborative cross mice, a genetically diverse population that mimics human genetic heterogeneity. Overall, this vaccine platform had variable efficacy in these populations supporting work to better tailor adjuvants to specific populations.

Abstract Image

广谱活性流感佐剂疫苗在免疫力低下和不同人群中的免疫原性
流感病毒爆发是全球每年的一大负担。由于病毒的抗原漂移/转移以及引起的免疫反应低下,目前的疫苗接种策略并不完善。使用经过计算优化的广谱抗原(COBRA)血凝素(HA)免疫原可以颠覆不断变异的病毒,但它们本身的免疫原性很差。为了提高亚单位疫苗的免疫原性,可以在疫苗中加入佐剂。例如,干扰素基因刺激物(STING)的激动剂已被证明可作为疫苗佐剂。然而,这些佐剂在最易感染流感病毒的高危人群中的应用尚未得到仔细研究。在这里,我们利用了一个疫苗平台,该平台由载入 COBRA HA 和 STING 激动剂环 GMP-AMP 的乙缩醛葡聚糖微颗粒组成。我们在肥胖、衰老和化疗引起的免疫抑制小鼠模型中检验了该平台的免疫原性。此外,我们还研究了合作杂交小鼠的疫苗疗效,这是一个模拟人类基因异质性的基因多样性群体。总体而言,该疫苗平台在这些人群中的效力各不相同,这为更好地为特定人群定制佐剂提供了支持。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Bioengineering & Translational Medicine
Bioengineering & Translational Medicine Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
8.40
自引率
4.10%
发文量
150
审稿时长
12 weeks
期刊介绍: Bioengineering & Translational Medicine, an official, peer-reviewed online open-access journal of the American Institute of Chemical Engineers (AIChE) and the Society for Biological Engineering (SBE), focuses on how chemical and biological engineering approaches drive innovative technologies and solutions that impact clinical practice and commercial healthcare products.
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