Progress in Respiratory Virus Vaccine Development

Alexander C. Schmidt, M.D.

Disclosures

Semin Respir Crit Care Med. 2007;28(2):243-252. 

In This Article

Abstract and Introduction

Viral respiratory infections continue to cause significant morbidity and mortality in infants and young children as well as in at-risk adults and the elderly. Although many viral pathogens are capable of causing acute respiratory disease, vaccine development has to focus on a limited number of pathogens (i.e., agents that commonly cause serious lower respiratory disease). Inactivated and, more recently, live attenuated influenza virus vaccines are the mainstay of interpandemic influenza prevention, but vaccines are not available yet for other important viruses such as respiratory syncytial virus, metapneumovirus, the parainfluenza viruses, and avian influenza viruses with pandemic potential. Reverse genetics systems that allow rational vaccine development are now widely used, and considerable progress has been made in preclinical and clinical development of novel respiratory virus vaccines.

The burden of acute respiratory infections (ARIs) caused by viral pathogens is impressive and leaves no doubt that effective and affordable vaccines are urgently needed.[1] With the exception of inactivated and live attenuated influenza virus vaccines, however, licensed vaccines to protect against viral ARIs are not available. The impact of respiratory viral infection is greatest in the very young, the elderly, and people with a suppressed or deficient immune system or with chronic conditions such as cardiopulmonary disease. Although repeated upper respiratory tract infections (URIs) are a normal part of growing up and essential for the maturation of the immune system, lower respiratory tract infections (LRIs) are less desirable, and LRIs are a common cause of hospital admission and excess mortality.[2–4] Respiratory syncytial virus (RSV) infection is the most frequent causative agent of a child's first LRI, and approximately one in a hundred healthy term infants is hospitalized with RSV bronchiolitis or pneumonia, often at an age as young as 2 to 4 months. Metapneumoviruses (MPVs), parainfluenza viruses (PIVs), and influenza viruses are other important causes of LRIs in infants, with PIV-3 and MPV causing LRI as early in life as RSV, whereas PIV-1, PIV-2, and influenza virus disease are more commonly seen in children over 6 months of age. PIV-1 and PIV-2 are common causes of URI and LRI in toddlers and in preschool children, with croup as the signature disease of PIV-1. Although RSV and MPV are on most pediatricians' minds, PIV-3 and influenza often go undiagnosed. Conversely, in adults with cardiopulmonary disease and in the elderly, influenza morbidity and mortality are common knowledge, whereas the burden of RSV disease is often underappreciated.[5] This overview on vaccine development focuses on RSV, MPV, the PIVs, and influenza viruses (i.e., members of the Paramyxo- and Orthomyxoviridae families). Vaccine development for rhinoviruses, adenoviruses, and coronaviruses will not be covered here, but several relevant reviews have recently been published.[6–9]

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