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

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          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.

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          Most cited references91

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          A newly discovered human pneumovirus isolated from young children with respiratory tract disease

          From 28 young children in the Netherlands, we isolated a paramyxovirus that was identified as a tentative new member of the Metapneumovirus genus based on virological data, sequence homology and gene constellation. Previously, avian pneumovirus was the sole member of this recently assigned genus, hence the provisional name for the newly discovered virus: human metapneumovirus. The clinical symptoms of the children from whom the virus was isolated were similar to those caused by human respiratory syncytial virus infection, ranging from upper respiratory tract disease to severe bronchiolitis and pneumonia. Serological studies showed that by the age of five years, virtually all children in the Netherlands have been exposed to human metapneumovirus and that the virus has been circulating in humans for at least 50 years.
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            Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children.

            We sought to determine the role of human metapneumovirus in lower respiratory tract illness in previously healthy infants and children. We tested nasal-wash specimens, obtained over a 25-year period from otherwise healthy children presenting with acute respiratory tract illness, for human metapneumovirus. A viral cause other than human metapneumovirus was determined for 279 of 687 visits for acute lower respiratory tract illness (41 percent) by 463 children in a population of 2009 infants and children prospectively seen from 1976 to 2001. There were 408 visits for lower respiratory tract illness by 321 children for which no cause was identified. Of these 321 children, specimens from 248 were available. Forty-nine of these 248 specimens (20 percent) contained human metapneumovirus RNA or viable virus. Thus, 20 percent of all previously virus-negative lower respiratory tract illnesses were attributable to human metapneumovirus, which means that 12 percent of all lower respiratory tract illnesses in this cohort were most likely due to this virus. The mean age of human metapneumovirus-infected children was 11.6 months, the male:female ratio was 1.8:1, 78 percent of illnesses occurred between December and April, and the hospitalization rate was 2 percent. The virus was associated with bronchiolitis in 59 percent of cases, pneumonia in 8 percent, croup in 18 percent, and an exacerbation of asthma in 14 percent. We also detected human metapneumovirus in 15 percent of samples from 261 patients with upper respiratory tract infection but in only 1 of 86 samples from asymptomatic children. Human metapneumovirus infection is a leading cause of respiratory tract infection in the first years of life, with a spectrum of disease similar to that of respiratory syncytial virus. Copyright 2004 Massachusetts Medical Society
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              Parainfluenza viruses.

              Human parainfluenza viruses (HPIV) were first discovered in the late 1950s. Over the last decade, considerable knowledge about their molecular structure and function has been accumulated. This has led to significant changes in both the nomenclature and taxonomic relationships of these viruses. HPIV is genetically and antigenically divided into types 1 to 4. Further major subtypes of HPIV-4 (A and B) and subgroups/genotypes of HPIV-1 and HPIV-3 have been described. HPIV-1 to HPIV-3 are major causes of lower respiratory infections in infants, young children, the immunocompromised, the chronically ill, and the elderly. Each subtype can cause somewhat unique clinical diseases in different hosts. HPIV are enveloped and of medium size (150 to 250 nm), and their RNA genome is in the negative sense. These viruses belong to the Paramyxoviridae family, one of the largest and most rapidly growing groups of viruses causing significant human and veterinary disease. HPIV are closely related to recently discovered megamyxoviruses (Hendra and Nipah viruses) and metapneumovirus.

                Author and article information

                Journal
                Pathogens
                Pathogens
                pathogens
                Pathogens
                MDPI
                2076-0817
                18 June 2020
                June 2020
                : 9
                : 6
                : 481
                Affiliations
                Department of Virology, Institute of Experimental Medicine, Saint Petersburg 197376, Russia; fedorova.iem@ 123456gmail.com (E.S.); matyshenko@ 123456iemspb.ru (V.M.); rudenko.lg@ 123456iemspb.ru (L.R.)
                Author notes
                Author information
                https://orcid.org/0000-0002-8670-8645
                https://orcid.org/0000-0002-0107-9959
                Article
                pathogens-09-00481
                10.3390/pathogens9060481
                7350342
                32570728
                59903b8c-ac13-440b-aa32-571edcd039df
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 07 May 2020
                : 16 June 2020
                Categories
                Review

                human metapneumovirus,hmpv vaccine,impaired immune responses,epitope-based vaccines,viral vectors,conserved hmpv epitopes,memory t cells

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