Younas S, Farooq S, Sahu S, Mwita RP, Özdemir Ö. Next-generation mucosal vaccines for respiratory viruses: Immunological correlates, platform design and clinical translation. World J Virol 2026; 15(1): 116939 [DOI: 10.5501/wjv.v15.i1.116939]
Corresponding Author of This Article
Öner Özdemir, MD, Professor, Department of Pediatric Allergy and Immunology, Faculty of Medicine, Sakarya University, Adnan Menderes Cad, Adapazarı 54100, Sakarya, Türkiye. ozdemir_oner@hotmail.com
Research Domain of This Article
Infectious Diseases
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Virol. Mar 25, 2026; 15(1): 116939 Published online Mar 25, 2026. doi: 10.5501/wjv.v15.i1.116939
Next-generation mucosal vaccines for respiratory viruses: Immunological correlates, platform design and clinical translation
Salma Younas, Soha Farooq, Sweta Sahu, Rhobi Peter Mwita, Öner Özdemir
Salma Younas, Department of Pharmacy, University of the Punjab, Lahore, Lahore 54000, Pakistan
Soha Farooq, Department of Pharmacy, Shifa Tameer e Millat University, Islamabad 44000, Pakistan
Sweta Sahu, J.J.M Medical College, Davangere 577004, Karnātaka, India
Rhobi Peter Mwita, Department of Pediatrics, Sakarya University, Sakarya 54100, Türkiye
Öner Özdemir, Department of Pediatric Allergy and Immunology, Faculty of Medicine, Sakarya University, Adapazarı 54100, Sakarya, Türkiye
Author contributions: Younas S and Özdemir O designed and supervised the study; Younas S, Farooq S, Mwita RP and Sahu S performed the literature search and data curation; Younas S and Farooq S drafted the initial manuscript; Younas S, Mwita RP and Özdemir O contributed to critical revision and methodological refinement; all authors contributed to data interpretation, reviewed and edited the manuscript, and approved the final version.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Öner Özdemir, MD, Professor, Department of Pediatric Allergy and Immunology, Faculty of Medicine, Sakarya University, Adnan Menderes Cad, Adapazarı 54100, Sakarya, Türkiye. ozdemir_oner@hotmail.com
Received: November 25, 2025 Revised: January 16, 2026 Accepted: February 10, 2026 Published online: March 25, 2026 Processing time: 108 Days and 21.8 Hours
Abstract
Influenza, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 continue to cause substantial morbidity and mortality. Currently licensed intramuscular (IM) vaccines effectively reduce severe disease and death but only partially suppress infection and transmission because they induce limited immunity in the respiratory mucosa. This minireview summarizes next-generation mucosal vaccines for respiratory viruses, focusing on the immunological correlates of protection, platform design, and clinical translation. The literature was identified through focused searches of PubMed and Scopus, prioritizing human studies and late-stage preclinical data published between 2000 and 2025. We outline the key mucosal immune correlates required to block viral entry at the airway epithelium, including secretory IgA and tissue-resident memory T cells, and review advances across major vaccine platforms. Current clinical experience with coronavirus disease 2019, influenza, and RSV mucosal vaccines is discussed, along with challenges related to immune measurement, delivery optimization, evaluation of transmission outcomes, and scalable global implementation, including heterologous systemic-mucosal prime-boost strategies. Overall, accumulating evidence positions mucosal vaccination as a promising complement to IM vaccines, with the potential to shift respiratory virus control from disease mitigation to prevention of infection and transmission.
Core Tip: Respiratory viruses initiate infections at mucosal surfaces; however, most licensed vaccines induce predominantly systemic immunity. Next-generation mucosal vaccines aim to generate protective immunity directly at the point of viral entry by inducing secretory IgA, tissue-resident memory T lymphocytes, and rapid innate immune responses in the respiratory tract. This review integrates key mucosal immune correlates with vaccine platform design, delivery strategies, and the emerging clinical evidence. We highlight the translational challenges and practical approaches.
