Prospects of and Barriers to the Development of Epitope-Based Vaccines against Human Metapneumovirus

Abstract

Human metapneumovirus (HMPV) is a major cause of respiratory illnesses in children, the elderly and immunocompromised patients. Although this pathogen was only discovered in 2001, an enormous amount of research has been conducted in order to develop safe and effective vaccines to prevent people from contracting the disease. In this review, we summarize current knowledge about the most promising experimental B- and T-cell epitopes of human metapneumovirus for the rational design of HMPV vaccines using vector delivery systems, paying special attention to the conservation of these epitopes among different lineages/genotypes of HMPV. The prospects of the successful development of an epitope-based HMPV vaccine are discussed in the context of recent findings regarding HMPV’s ability to modulate host immunity. In particular, we discuss the lack of data on experimental human CD4 T-cell epitopes for HMPV despite the role of CD4 lymphocytes in both the induction of higher neutralizing antibody titers and the establishment of CD8 memory T-cell responses. We conclude that current research should be focused on searching for human CD4 T-cell epitopes of HMPV that can help us to design a safe and cross-protective epitope-based HMPV vaccine.

Characterization of prefusion-F-specific antibodies elicited by natural infection with human metapneumovirus

“…However, reinfections among the immunocompromised and older adults can lead to more severe disease such as bronchiolitis and pneumonia (Boivin et al, 2002(Boivin et al, , 2007Walsh et al, 2008). Although vaccines and monoclonal antibodies are in various stages of early clinical development (Biacchesi et al, 2005;Chupin et al, 2021;Cox et al, 2014;Cseke et al, 2007;Hamelin et al, 2007;Herfst et al, 2008;Huang et al, 2021;Karron et al, 2018;Levy et al, 2013;Olmedillas et al, 2018;Schuster et al, 2015;Stepanova et al, 2020;Stewart-Jones et al, 2021), there are currently no US FDA-approved interventions available. To develop an effective hMPV countermeasure, it will be important to have a thorough understanding of the humoral immune response that is elicited by natural infection.…”

Development of a novel multi-epitope mRNA vaccine candidate to combat HMPV virus

“… 52 , 53 Meanwhile, most identified epitopes are located on F protein, the use of the F protein alone can induce the production of protective monoclonal antibodies, while currently no other proteins have been found to generate neutralizing antibodies. 54 , 55 However, proteins other than F are also involved in immune response, SH can inhibit the secretion of inflammatory cytokines, while G protein has the ability to decrease innate immune responses. Although viruses lacking G and SH proteins can still replicate, their replication efficiency will be greatly reduced.…”

A chimeric influenza virus vaccine expressing fusion protein epitopes induces protection from human metapneumovirus challenge in mice

“…Several studies have reported that many HMPV vaccines exhibit immune damage problems, such as enhanced disease and delayed viral clearance due to excessive activation of Th2-type immune responses in animal experiments( Schickli et al, 2009 ; Anderson, 2013 ; Aerts et al, 2015 ). In our study, we evaluated recombinant virus-induced immune response phenotypes by some popular representative factors of Th1-type and Th2-type immune responses( Dubois et al, 2019 ; Stepanova et al, 2020 ). rFLU-HMPV/F-NS activated Th1/Th2 type immune responses in vivo and favored Th1 type cellular immune responses, inducing a Th1/Th2 type balance.…”

“…An effective HMPV vaccine would ensure the induction of a prompt and appropriate immune response (generation of immune memory) following natural HMPV infection of the host ( Herd et al, 2006 ; Ren et al, 2015 ). Accurate stimulation of CD4 T cells to increase antibody production following vaccine immunization and the formation of a rapid and effective secondary CTL response of CD8 memory T cells to natural HMPV infection are key issues in the study of effective HMPV vaccines ( Hamelin et al, 2007 ; Kolli et al, 2008 ; González et al, 2017 ; Stepanova et al, 2020 ). Therefore, studying the CD4 branch of HMPV immunity is a key requirement for controlling the pathological process of HMPV and developing prevention strategies.…”