Academic journal article Journal of Health Population and Nutrition

Rotavirus Serotypes: Classification and Importance in Epidemiology, Immunity, and Vaccine Development

Academic journal article Journal of Health Population and Nutrition

Rotavirus Serotypes: Classification and Importance in Epidemiology, Immunity, and Vaccine Development

Article excerpt

INTRODUCTION

Diarrhoeal diseases continue to be a significant cause of morbidity of infants and young children in developed countries. It is also a significant cause of morbidity and mortality in the same age group in developing countries. There is a universal agreement that rotaviruses are the single most important aetiologic agents of severe diarrhoeal illnesses of infants and young children worldwide. Although repeated rotaviral infections occur throughout an individual's lifetime, symptomatic infections occur most commonly during the first two years of life.

Rotaviruses are estimated to cause over 800,000 deaths annually in children aged less than 5 years in developing countries, and are responsible for over 500,000 visits to a medical practitioner annually in the U.S.A. alone (1,2). Hence, major emphasis has been placed on the development of a safe and effective vaccine for use in early infancy. After over two decades of development, the first rotavirus vaccine (live oral rhesus monkey rotavirus-based quadrivalent vaccine [RotaShield]) was approved by the U.S. Food and Drug Administration for use in a 3-dose regimen in infants at 2, 4, and 6 months of age (1). The success of this livere-assortant vaccine has relied on two major principles: a Jennerian approach by which (i) an animal rotavirus strain (rhesus monkey) confers attenuation, and (ii) outer-capsid proteins induce antibodies to epidemiologically important serotypes. In this invited commentary, we describe the rationale for the importance of defining rotavirus serotypes.

In many viral diseases, neutralizing antibodies appear to play an important role in protection against diseases and/or infections in a type-specific manner. For example, each of the poliovirus serotypes (type 1, 2, and 3) are incorporated in both the live and inactivated poliovirus vaccines. Similarly, the emergence of novel or unusual serotype(s) of an influenza virus is carefully monitored globally to be ready to detect such a virus, analyze its antigenic composition, and prepare a vaccine carrying appropriate serotype specificities. In this regard, there has been surveillance of rotavirus serotypes in most parts of the world to understand their geographic and temporal distribution to establish the importance of each serotype as a prelude to vaccine development and, in addition, to gain insights into the immune mechanisms of protection. Before delving into the serotypic specificity of rotavirus, we should consider some basic properties of this virus.

Rotavirus: classification, structure, and antigenic composition

Rotavirus, which constitutes a genus within the Reoviridae family, is a medium-sized (70 nm) non-enveloped virus. The mature particle consists of a tripleshelled capsid consisting of the outer, intermediate, and inner layers. The outer capsid contains two proteins (VP4 and VP7), whereas the intermediate layer is formed by VP6, and the inner by VP2 which encloses two other proteins VP1 and VP3, as well as the viral genome consisting of 11 segments of double-stranded RNA, the latter encoding six structural and six non-structural proteins (2,2a,3). Because of the segmented nature of the rotavirus genome, genetic reassortment occurs at high frequency during mixed infection.

Rotaviruses carry three important antigenic specificities: group, subgroup, and serotype. Based on group specificity which is conferred predominantly by VP6, rotaviruses are divided into 7 groups (A to G). Human rotavirus (HRV)-associated infections are predominantly caused by group A, and less commonly by group B or C, and thus, the emphasis of vaccine development has been targeted at group A rotavirus-associated disease. Of note is the finding that group B rotavirus (adult diarrhoea rotavirus [ADRV]) which caused large outbreaks in China in the 1980s was recently (1997 and 1998) detected in patients with diarrhoea in India, marking the first emergence of group B ADRV outside China (4). …

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