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  • Review Article
  • Published:

Rotavirus vaccines: recent developments and future considerations

Nature Reviews Microbiology volume 5, pages 529–539 (2007)Cite this article

Key Points

  • Rotaviruses are the single most important aetiological agent of severe gastroenteritis in children. They are responsible for the death of approximately 1,600 children each day worldwide, mostly in developing countries.

  • Two new rotavirus vaccines have recently been shown to be safe and effective in protecting young children against severe rotavirus gastroenteritis.

  • These vaccines were designed using different approaches: the first (Rotarix) is an attenuated human rotavirus that is representative of the most frequently circulating rotaviruses. The second (RotaTeq) is composed of five rotavirus strains, which are all derived from a parental bovine rotavirus strain and contain a gene from rotaviruses of human origin.

  • Ongoing clinical trials will be key in determining whether these two vaccines are efficacious in the poorest areas of the world, where they are most needed. As for other vaccines, post-marketing studies are ongoing to round up the efficacy and safety profile of the vaccines.

  • Improvement of the two new vaccines and development of the next generation of rotavirus vaccines is hampered by our limited knowledge of the mechanisms of rotavirus pathogenesis and the basis for protection against rotavirus-associated gastroenteritis.

  • Studies of the rotavirus mucosal immune response, and in general of the immune response of children, will be important for the development of correlates of protection for rotavirus vaccines.

Abstract

Two new vaccines have recently been shown to be safe and effective in protecting young children against severe rotavirus gastroenteritis. Although both vaccines are now marketed worldwide, it is likely that improvements to these vaccines and/or the development of future generations of rotavirus vaccines will be desirable. This Review addresses recent advances in our knowledge of rotavirus, the host immune response to rotavirus infection and the efficacy and safety of the new vaccines that will be helpful for improving the existing rotavirus vaccines, or developing new rotavirus vaccines in the future.

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Figure 1: Rotavirus.
Figure 2: Potential mechanisms of rotavirus pathogenesis and immunity.
Figure 3: The Rotarix and Rotateq vaccines.

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  1. Instituto de Genética Humana, Pontificia Universidad Javeriana, Carrera 7, Bogotá, 40–62, Colombia

    Juana Angel & Manuel A. Franco

  2. Stanford University School of Medicine, Alway Building, Room M121, 300 Pasteur Drive, Stanford, 94305-5119, California, USA

    Harry B. Greenberg

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Juana Angel and Manuel Franco were co-principal investigators for a trial of the RIX4414 rotavirus vaccine (the precursor to the Rotarix vaccine), that was partially funded by GlaxoSmithKline.

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Glossary

Host-range restriction

(HRR). The limited capacity of certain viruses to grow and transmit efficiently in an animal species that is distinct (heterologous) from the animal species they naturally infect (homologous).

Intussusception

A pathological event in which the intestine acutely invaginates upon itself and becomes obstructed, followed by local necrosis of gut tissue.

Reverse genetics

A method that allows the production of viruses that possess genes derived from cloned cDNA.

Small interfering RNAs

Small antisense RNAs (20–25 nucleotides long) that are generated from specific double-stranded RNAs that trigger RNA interference.

CD8+ T cells

A subpopulation of T cells that express the CD8 receptor. CD8+ cells recognize antigens that are presented on the surface of host cells by major histocompatibility complex (MHC) class I molecules, leading to their destruction, and are therefore also known as cytotoxic T cells.

CD4+ T cells

A subpopulation of T cells that express the CD4 receptor. CD4+ cells recognize antigens that are presented on the surface of host cells by major histocompatibility complex (MHC) class II molecules. These cells aid in immune responses and are therefore referred to as T-helper cells.

Extra hepatic biliary atresia

A disease of infancy that is characterized by inflammation and fibrosis of the extrahepatic biliary tract, resulting in cirrhosis.

ELISPOT

An enzyme-linked immunoassay to identify individual cells that secrete a particular molecule.

Antigenaemia

The presence of viral antigens in the blood.

Parenteral

A vaccine administered by injection into the muscle, subcutaneous tissue or dermis (as opposed to mucosal immunization via an oral or nasal route).

Jennerian vaccines

Vaccines derived from microorganisms that infect animals and which are naturally attenuated in humans owing to host-range restriction.

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Angel, J., Franco, M. & Greenberg, H. Rotavirus vaccines: recent developments and future considerations. Nat Rev Microbiol 5, 529–539 (2007). https://doi.org/10.1038/nrmicro1692

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