Current Perspectives and Future Directions in the Immunogenicity Landscape of Norovirus Vaccines

Résumé fourni par la source

IntroductionHuman norovirus (HuNoV) is a leading cause of acute viral gastroenteritis worldwide, accounting for approximately 685 million total cases annually [1][2][3].The virus was first identified following an outbreak of gastroenteritis in Norwalk, Ohio, USA, in 1968 and subsequently named the Norwalk virus in 1972 [4].Advances in molecular biology, such as gene cloning and sequencing, later revealed that norovirus, along with other related viruses, belongs to the Caliciviridae family, sharing a similar genome organization [5].Norovirus is highly contagious, readily transmitted through contaminated food or water, direct contact with infected individuals, or exposure to contaminated surfaces [1].Its low infectious dose and environmental persistence facilitate rapid spread, especially in communal settings such as schools, hospitals, and long-term care facilities, making outbreaks difficult to control [2, 3].As a result, norovirus imposes a substantial global health and economic burden [4][5][6].Human norovirus infects people of all ages, but it has the greatest impact on young children and the elderly.Both groups are more susceptible to severe symptoms, complications, hospitalizations, and, in rare cases, death.Each year, there are an estimated 685 million total cases of acute gastroenteritis caused by norovirus, of which 200 million cases of norovirus occur worldwide among children under 5 (Fig. 1), leading to about 50,000 child deaths, with the vast majority occurring in developing and low-income countries [7].By age 5, approximately 1 in 40 children will visit an emergency room, and 1 in 160 will be hospitalized due to norovirus illness.Most norovirus-associated hospitalizations and deaths (136,000 to 278,000 deaths worldwide annually) occur among adults aged 65 years and older.Elderly adults not only experience more severe disease but also have longer symptom duration and a higher risk of complications like dehydration, sepsis, or cardiac events, especially Human norovirus (HuNoV) is a leading cause of acute gastroenteritis worldwide, causing severe illness and death in vulnerable populations, including infants and the elderly.Despite advances in norovirus vaccine candidates such as virus-like particles (VLPs), adenovirus-based oral vaccines, and mRNA vaccines, no vaccine has been approved yet.Current clinical trials primarily target the GI.1 and GII.4 genotypes responsible for most outbreaks.However, the extensive genetic diversity of HuNoV, along with continual antigenic evolution, poses significant challenges for developing broadly protective vaccines.Recent advances in experimental tools, including human intestinal enteroid cultures and surrogate neutralization assays, have improved norovirus vaccine efficacy assessment.Nevertheless, the lack of robust culture systems and animal models that faithfully mimic human infection continues to limit comprehensive evaluation of immune responses to diverse variants.Moreover, standardized correlates of protection, particularly those addressing mucosal immunity critical for infection prevention, remain to be established.This review integrates current immunogenicity assessment methodologies and evaluates ongoing HuNoV vaccine strategies, with emphasis on variant strain selection and platform technologies.We discuss key challenges related to population diversity, immune imprinting, and the complex interplay between systemic and mucosal immune responses as influenced by vaccine delivery routes and adjuvant formulations.By integrating recent advances in vaccine platforms, immunological tools, and delivery strategies, this review provides a framework for addressing critical obstacles in norovirus vaccine development.Such integrative perspectives are crucial for developing safe, effective, and broadly protective vaccines that offer meaningful benefits to global health.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.