Developing a liquid formulation for CVXGA1 COVID-19 intranasal vaccine

开发CVXGA 1 COVID-19鼻内疫苗的液体制剂 摘要 在这项I期SBIR申请中，我们建议开发一种用于CVXGA 1 COVID-19鼻内给药的液体制剂 疫苗持续的2019年全球冠状病毒病（COVID-19）大流行导致许多人丧生， 生命和社会经济的破坏。具有较高传播率和逃避疫苗接种能力的变异体， 自然感染引起的宿主免疫反应不断出现，导致突破性进展 尽管有额外的加强剂量。下一代COVID-19疫苗，也可以获得 对于发展中国家来说，需要阻止SARS-COV-2的传播。副流感病毒5型（PIV 5）是 一种用于表达外源抗原以对抗许多病毒和细菌病原体的优良病毒载体。单个 用CVXGA 1（表达SARS-CoV-2 S蛋白的PIV 5）鼻内免疫诱导粘膜，体液， 和细胞免疫应答，在小鼠，仓鼠， 雪貂、猫和非洲绿色猴。CVXGA 1也阻断了接触传播。CVXGA 1疫苗 目前正在进行I期临床研究（NCT 04954287）。目前的CVXGA 1疫苗是在蔗糖中配制的 磷酸谷氨酰胺（SPG）缓冲液，在-80 ℃和-20 ℃下稳定，但在4 ℃下不稳定。4 ℃稳定 液体制剂对于将这种鼻内疫苗用于全球免疫至关重要。我们建议 鉴定可在4 ℃下提供CVXGA 1稳定性至少4个月的制剂。我们建议 首先优化CVXGA 1储存的pH值，然后筛选多种赋形剂，以选择至少两种铅 用于进一步表征的制剂，包括免疫原性研究。第二阶段SBIR提案将 重点关注CVXGA 1在所选给药装置（如预充式喷雾器）和疫苗中的长期储存 储存后评估。

Developing a liquid formulation for CVXGA1 COVID-19 intranasal vaccine ABSTRACT In this Phase I SBIR application, we propose to develop a liquid formulation for CVXGA1 COVID-19 intranasal vaccine. The ongoing global coronavirus disease 2019 (COVID-19) pandemic has resulted in the loss of many lives and social economic disruptions. Variants with higher transmission rates and ability to evade vaccine or natural infection elicited host immune responses have continuously emerged leading to breakthrough infections despite additional booster doses. The next generation of COVID-19 vaccine, that is also accessible to the developing countries, is needed to stop SARS-COV-2 transmission. Parainfluenza virus type 5 (PIV5) is an excellent viral vector for expressing foreign antigens to fight many viral and bacterial pathogens. A single intranasal immunization with CVXGA1 (PIV5 expressing SARS-CoV-2 S protein) induces mucosal, humoral, and cellular immune responses, providing protection against SARS-CoV-2 challenge in mice, hamsters, ferrets, cats, and Africa green monkeys. CVXGA1 also blocked contact transmission. CVXGA1 vaccine is currently in phase 1 clinical studies (NCT04954287). The current CVXGA1 vaccine is formulated in sucrose phosphate glutamine (SPG) buffer which is stable at -80 oC and -20 oC but not stable at 4 oC. The 4 oC stable liquid formulation is critical to the launch of this intranasal vaccine for global immunization. We propose to identify a formulation which can provide CVXGA1 stability at 4 oC for a minimum of 4 months. We propose to first optimize the pH for CVXGA1 storage, then screen multiple excipients to select at least two lead formulations for further characterization, including immunogenicity studies. The Phase II SBIR proposal will focus on long-term storage of CVXGA1 in the chosen dose device (such as prefilled sprayer) and vaccine evaluation after storage.