Center for Vaccines and Immunology, University of Georgia, Athens, GA, USA.
Department of Infectious Diseases, University of Georgia, Athens, GA, USA.
Sci Rep. 2024 Jun 14;14(1):13800. doi: 10.1038/s41598-024-64351-7.
Adjuvants enhance, prolong, and modulate immune responses by vaccine antigens to maximize protective immunity and enable more effective immunization in the young and elderly. Most adjuvants are formulated with injectable vaccines. However, an intranasal route of vaccination may induce mucosal and systemic immune responses for enhancing protective immunity in individuals and be easier to administer compared to injectable vaccines. In this study, a next generation of broadly-reactive influenza hemagglutinin (HA) vaccines were developed using the Computationally Optimized Broadly Reactive Antigen (COBRA) methodology. These HA vaccines were formulated with Mastoparan 7 (M7-NH) mast cell degranulating peptide adjuvant and administered intranasally to determine vaccine-induced seroconversion of antibodies against a panel of influenza viruses and protection following infection with H1N1 and H3N2 viruses in mice. Mice vaccinated intranasally with M7-NH-adjuvanted COBRA HA vaccines had high HAIs against a panel of H1N1 and H3N2 influenza viruses and were protected against both morbidity and mortality, with reduced viral lung titers, following challenge with an H1N1 influenza virus. Additionally, M7-NH adjuvanted COBRA HA vaccines induced Th2 skewed immune responses with robust IgG and isotype antibodies in the serum and mucosal lung lavages. Overall, this intranasally delivered M7-NH -adjuvanted COBRA HA vaccine provides effective protection against drifted H1N1 and H3N2 viruses.
佐剂通过疫苗抗原增强、延长和调节免疫反应，以最大限度地提高保护免疫力，并使年轻人和老年人更有效地进行免疫接种。大多数佐剂都是与注射用疫苗一起配制的。然而，鼻腔接种途径可以诱导黏膜和全身免疫反应，增强个体的保护免疫力，并且与注射用疫苗相比更容易给药。在这项研究中，使用计算优化的广泛反应性抗原（COBRA）方法开发了新一代广泛反应性流感血凝素（HA）疫苗。这些 HA 疫苗与 Mastoparan 7（M7-NH）肥大细胞脱颗粒肽佐剂一起配制，并通过鼻腔给药，以确定针对一系列流感病毒的抗体血清转化率以及在感染 H1N1 和 H3N2 病毒后对小鼠的保护作用。用 M7-NH 佐剂的 COBRA HA 疫苗鼻腔接种的小鼠对一系列 H1N1 和 H3N2 流感病毒具有高血凝素抑制抗体（HAI），并且在感染 H1N1 流感病毒后，在发病率和死亡率方面得到保护，肺部病毒载量减少。此外，M7-NH 佐剂的 COBRA HA 疫苗诱导 Th2 偏向的免疫反应，在血清和黏膜肺灌洗液中产生强大的 IgG 和同种型抗体。总体而言，这种鼻腔给药的 M7-NH 佐剂的 COBRA HA 疫苗提供了针对漂移的 H1N1 和 H3N2 病毒的有效保护。
