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      A review of vaccine research and development: Human acute respiratory infections ☆

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          Abstract

          Worldwide, acute respiratory infections (ARIs) constitute the leading cause of acute illnesses, being responsible for nearly 4 million deaths every year, mostly in young children and infants in developing countries. The main infectious agents responsible for ARIs include influenza virus, respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV-3), Streptococcus pneumoniae and Haemophilus influenzae. While effective vaccines against influenza, H. influenzae type b (Hib) and S. pneumoniae infections have been available for several years, no vaccine is available at present against illnesses caused by RSV, PIV-3, metapneumovirus or any of the three novel coronaviruses. In addition, the threat constituted by the multiple outbreaks of avian influenza during the last few years is urgently calling for the development of new influenza vaccines with broader spectrum of efficacy, which could provide immunity against an avian influenza virus pandemic. This article reviews the state of the art in vaccine R&D against ARIs and attempts to address these basic public health questions.

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

          Bernadette van den Hoogen, Jan C de Jong, Jan Groen … (2001)
          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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            Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia.

            Patrick C. Y. Woo, Susanna Lau, Chung-ming Chu … (2005)
            Despite extensive laboratory investigations in patients with respiratory tract infections, no microbiological cause can be identified in a significant proportion of patients. In the past 3 years, several novel respiratory viruses, including human metapneumovirus, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and human coronavirus NL63, were discovered. Here we report the discovery of another novel coronavirus, coronavirus HKU1 (CoV-HKU1), from a 71-year-old man with pneumonia who had just returned from Shenzhen, China. Quantitative reverse transcription-PCR showed that the amount of CoV-HKU1 RNA was 8.5 to 9.6 x 10(6) copies per ml in his nasopharyngeal aspirates (NPAs) during the first week of the illness and dropped progressively to undetectable levels in subsequent weeks. He developed increasing serum levels of specific antibodies against the recombinant nucleocapsid protein of CoV-HKU1, with immunoglobulin M (IgM) titers of 1:20, 1:40, and 1:80 and IgG titers of <1:1,000, 1:2,000, and 1:8,000 in the first, second and fourth weeks of the illness, respectively. Isolation of the virus by using various cell lines, mixed neuron-glia culture, and intracerebral inoculation of suckling mice was unsuccessful. The complete genome sequence of CoV-HKU1 is a 29,926-nucleotide, polyadenylated RNA, with G+C content of 32%, the lowest among all known coronaviruses with available genome sequence. Phylogenetic analysis reveals that CoV-HKU1 is a new group 2 coronavirus. Screening of 400 NPAs, negative for SARS-CoV, from patients with respiratory illness during the SARS period identified the presence of CoV-HKU1 RNA in an additional specimen, with a viral load of 1.13 x 10(6) copies per ml, from a 35-year-old woman with pneumonia. Our data support the existence of a novel group 2 coronavirus associated with pneumonia in humans.
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              Estimates of world-wide distribution of child deaths from acute respiratory infections.

              Brian Williams, Eleanor Gouws, Cynthia Boschi-Pinto … (2002)
              Acute respiratory infections (ARI) are among the leading causes of childhood mortality. Estimates of the number of children worldwide who die from ARI are needed in setting priorities for health care. To establish a relation between deaths due to ARI and all-cause deaths in children under 5 years we show that the proportion of deaths directly attributable to ARI declines from 23% to 18% and then 15% (95% confidence limits range from +/- 2% to +/- 3%) as under-5 mortality declines from 50 to 20 and then to 10/1000 per year. Much of the variability in estimates of ARI in children is shown to be inherent in the use of verbal autopsies. This analysis suggests that throughout the world 1.9 million (95% CI 1.6-2.2 million) children died from ARI in 2000, 70% of them in Africa and southeast Asia.
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                Author and article information

                Contributors
                Marc P. Girard
                Marie Paule Kieny
                Journal
                Journal ID (nlm-ta): Vaccine
                Journal ID (iso-abbrev): Vaccine
                Title: Vaccine
                Publisher: Published by Elsevier Ltd.
                ISSN (Print): 0264-410X
                ISSN (Electronic): 1873-2518
                Publication date PMC-release: 3 August 2005
                Publication date (Print): 30 December 2005
                Publication date (Electronic): 3 August 2005
                Volume: 23
                Issue: 50
                Pages: 5708-5724
                Affiliations
                [a ]University Paris 7, UFR Biochemistry, 39 rue Seignemartin, FR 69008 Lyon, France
                [b ]Initiative for Vaccine Research, World Health Organization, 20 Avenue Appia, CH 1211-Genève 27, Switzerland
                Author notes
                [* ]Corresponding author. Tel.: +33 4 7874 8531. marc.girard36@ 123456wanadoo.fr
                [1]

                Tel.: +41 22 791 35 91.

                Article
                Publisher ID: S0264-410X(05)00718-8
                DOI: 10.1016/j.vaccine.2005.07.046
                PMC ID: 7130922
                PubMed ID: 16154667
                SO-VID: 8d69624b-5183-4b36-9121-b8984b0d05ce
                Copyright © Copyright © 2005 Published by Elsevier Ltd.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 16 May 2005
                Date accepted : 22 July 2005
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                Subject: Article

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: vaccines,sars,influenza,pneumococcal infection,streptococcus pneumoniae,haemophilus influenzae,hib,respiratory syncitial virus,rsv,parainfluenza viruses,piv,bronchiolitis
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: vaccines, sars, influenza, pneumococcal infection, streptococcus pneumoniae, haemophilus influenzae, hib, respiratory syncitial virus, rsv, parainfluenza viruses, piv, bronchiolitis

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