Progress and challenges in the clinical evaluation of immune responses to respiratory mucosal vaccines

ABSTRACT

Introduction

Following the coronavirus disease pandemic, respiratory mucosal vaccines that elicit both mucosal and systemic immune responses have garnered increasing attention. However, human physiological characteristics pose significant challenges in the evaluation of mucosal immunity, which directly impedes the development and application of respiratory mucosal vaccines.

Areas Covered

This study summarizes the characteristics of immune responses in the respiratory mucosa and reviews the current status and challenges in evaluating immune response to respiratory mucosal vaccines.

Expert Opinion

Secretory Immunoglobulin A (S-IgA) is a major effector molecule at mucosal sites and a commonly used indicator for evaluating respiratory mucosal vaccines. However, the unique physiological structure of the respiratory tract pose significant challenges for the clinical collection and detection of S-IgA. Therefore, it is imperative to develop a sampling method with high collection efficiency and acceptance, a sensitive detection method, reference materials for mucosal antibodies, and to establish a threshold for S-IgA that correlates with clinical protection. Sample collection is even more challenging when evaluating mucosal cell immunity. Therefore, a mucosal cell sampling method with high operability and high tolerance should be established. Targets of the circulatory system capable of reflecting mucosal cellular immunity should also be explored.

KEYWORDS:

• Respiratory tract
• mucosal vaccine
• mucosal antibody
• mucosal cellular immunity
• clinical evaluation

Article highlights

• Respiratory mucosal vaccines, which can elicit both mucosal and systemic immune responses, have garnered increasing attention.

• Currently, four influenza mucosal vaccines have been approved for marketing and five COVID-19 mucosal vaccines have been approved for emergency use. Clinical studies have confirmed the efficacy of respiratory mucosal vaccines.

• The complexity of mucosal immunity and uniqueness of its physiological structure impedes the evaluation of mucosal immune responses, thus limiting the development and application of mucosal vaccines.

• The unique physiological structure and low levels of antibodies in the respiratory tract pose challenges for the detection of S-IgA, a crucial effector molecule in the mucosa. To address this, standard sampling methods, sensitive detection method, and reference materials should be established, along with an investigation of the clinical protection threshold associated with S-IgA.

• Obtaining clinical samples for mucosal cellular immunity evaluation poses significant challenges. A highly efficient and acceptable method for sample collection should be established

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Xuanxuan Zhang, Jialu Zhang and Si Chen conceived and drafted the manuscript; Qian He, Yu Bai, Jianyang Liu, Zhongfang Wang, Zhenglun Liang provided valuable discussion; Ling Chen, Qunying Mao and Miao Xu revised the manuscript. All authors have read and approved the article.

Additional information

Funding

This research was supported by R&D Program of Guangzhou National Laboratory, Grant No. SRPG23-005.