Rotavirus vaccines: Recent developments and future considerations

Stanford University, Stanford, California, United States
Nature Reviews Microbiology (Impact Factor: 23.57). 08/2007; 5(7):529-39. DOI: 10.1038/nrmicro1692
Source: PubMed

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.

Download full-text

Full-text

Available from: Harry B Greenberg
  • Source
    • "parenteral injection of non-replicating vaccines may result in mucosal protection mediated by the induction and transudation of antibodies into the gut. The high titers of circulating anti-rotavirus antibodies transmitted transplacentally in humans appear to both modulate the take of live oral vaccines and be protective against early rotavirus disease [10] [11] [12] [13]. Furthermore, passively administered antibody may prevent or diminish rotavirus disease [6] [14]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The P2-VP8 subunit vaccine for the prevention of rotavirus gastroenteritis is comprised of a truncated VP8 subunit protein from the rotavirus Wa strain (G1[P8]) fused to the tetanus toxin P2 epitope, and adsorbed on aluminum hydroxide for intramuscular administration. Three groups of 16 adults were randomized to receive three injections of P2-VP8 (12) or placebo (4) at doses of 10, 30 or 60μg of vaccine. IgG and IgA antibodies to P2-VP8 were assessed by ELISA in serum and lymphocyte supernatant (ALS). Serum samples were tested for neutralizing antibodies to homologous and heterologous strains of rotavirus. The vaccine was well-tolerated. All vaccine recipients demonstrated significant IgA responses and all but one demonstrated IgG responses; in the 60μg cohort, geometric mean titers (GMTs) rose 70- and 80-fold for IgA and IgG, respectively. Homologous neutralizing antibody responses were observed in about half of participants in all three dose cohorts; in the 60μg cohort, GMTs against Wa rose from 128 to 992. Neutralizing antibody responses were robust to P[8] strains, moderate to P[4] strains and negligible to P[6] strains. ALS IgA responses were dose dependent. The P2-VP8 subunit vaccine was well tolerated and evoked promising immune responses. NCT01764256. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Jun 2015 · Vaccine
  • Source
    • "Majority of rotavirus infection-associated mortality occurs in the developing countries. Nonetheless, nearly 1 in 80 children is hospitalized with rotavirus gastroenteritis by 5 years of age in the US [1] [2] [3]. Since there are no specific antiviral agent for rotavirus infection, the treatment options for rotavirus infection are limited to providing oral rehydration solution to restore and maintain hydration until the infection resolves [4]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recently our group has demonstrated that cellular triglycerides (TG) levels play an important role in rotavirus replication. In this study, we further examined the roles of the key enzymes for TG synthesis (lipogenesis) in the replication of rotaviruses by using inhibitors of fatty acid synthase, long chain fatty acid acyl-CoA synthetase (ACSL), and diacylglycerol acyltransferase and acyl-CoA:cholesterol acyltransferase in association with lipid droplets of which TG is a major component. Triacsin C, a natural ACSL inhibitor from Streptomyces aureofaciens, was found to be highly effective against rotavirus replication. Thus, novel triacsin C analogs were synthesized and evaluated for their efficacies against the replication of rotaviruses in cells. Many of the analogs significantly reduced rotavirus replication, and one analog (1e) was highly effective at a nanomolar concentration range (ED 50 0.1 μM) with a high therapeutic index in cell culture. Our results suggest a crucial role of lipid metabolism in rotavirus replication, and triacsin C and/or its analogs as potential therapeutic options for rotavirus infections.
    Full-text · Article · Apr 2013 · European Journal of Medicinal Chemistry
  • Source
    • "Majority of rotavirus infection-associated mortality occurs in the developing countries. Nonetheless, nearly 1 in 80 children is hospitalized with rotavirus gastroenteritis by 5 years of age in the US [1] [2] [3]. Since there are no specific antiviral agent for rotavirus infection, the treatment options for rotavirus infection are limited to providing oral rehydration solution to restore and maintain hydration until the infection resolves [4]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recently our group has demonstrated that cellular triglycerides (TG) levels play an important role in rotavirus replication. In this study, we further examined the roles of the key enzymes for TG synthesis (lipogenesis) in the replication of rotaviruses by using inhibitors of fatty acid synthase, long chain fatty acid acyl-CoA synthetase (ACSL), and diacylglycerol acyltransferase and acyl-CoA:cholesterol acyltransferase in association with lipid droplets of which TG is a major component. Triacsin C, a natural ACSL inhibitor from Streptomyces aureofaciens, was found to be highly effective against rotavirus replication. Thus, novel triacsin C analogs were synthesized and evaluated for their efficacies against the replication of rotaviruses in cells. Many of the analogs significantly reduced rotavirus replication, and one analog (1e) was highly effective at a nanomolar concentration range (ED 50 0.1 μM) with a high therapeutic index in cell culture. Our results suggest a crucial role of lipid metabolism in rotavirus replication, and triacsin C and/or its analogs as potential therapeutic options for rotavirus infections.
    Full-text · Article · Apr 2013 · European Journal of Medicinal Chemistry
Show more

Similar Publications