Biomedical & Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA.
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.
FASEB J. 2022 Mar;36(3):e22182. doi: 10.1096/fj.202101703R.
Pre-pandemic influenza H5N1 vaccine has relatively low immunogenicity and often requires high antigen amounts and two immunizations to induce protective immunity. Incorporation of vaccine adjuvants is promising to stretch vaccine doses during pandemic outbreaks. This study presents a physical radiofrequency (RF) adjuvant (RFA) to conveniently and effectively increase the immunogenicity and efficacy of H5N1 vaccine without modification of vaccine preparation. Physical RFA is based on a brief RF treatment of the skin to induce thermal stress to enhance intradermal vaccine-induced immune responses with minimal local or systemic adverse reactions. We found that physical RFA could significantly increase H5N1 vaccine-induced hemagglutination inhibition antibody titers in murine models. Intradermal H5N1 vaccine in the presence of RFA but not vaccine alone significantly lowered lung viral titers, reduced body weight loss, and improved survival rates after lethal viral challenges. The improved protection in the presence of RFA was correlated with enhanced humoral and cellular immune responses to H5N1 vaccination in both male and female mice, indicating no gender difference of RFA effects in murine models. Our data support further development of the physical RFA to conveniently enhance the efficacy of H5N1 vaccine.
大流行前的 H5N1 流感疫苗的免疫原性相对较低，通常需要高剂量抗原和两次免疫接种才能诱导保护性免疫。在大流行爆发期间，疫苗佐剂的结合有望延长疫苗剂量。本研究提出了一种物理射频（RF）佐剂（RFA），可方便有效地提高 H5N1 疫苗的免疫原性和功效，而无需对疫苗制备进行修饰。物理 RFA 基于皮肤的短暂射频处理，以诱导热应激，从而增强皮内疫苗诱导的免疫反应，而局部或全身不良反应最小。我们发现，物理 RFA 可显著提高小鼠模型中 H5N1 疫苗诱导的血凝抑制抗体滴度。在存在 RFA 的情况下，皮内 H5N1 疫苗而不是单独的疫苗可显著降低肺部病毒滴度、减轻体重减轻，并提高致命病毒攻击后的存活率。RFA 存在时改善的保护与 H5N1 疫苗接种后体液和细胞免疫反应的增强相关，这表明 RFA 对小鼠模型的影响没有性别差异。我们的数据支持进一步开发物理 RFA 以方便地增强 H5N1 疫苗的功效。
