Vaccines against rotavirus and human papillomavirus (HPV).
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OBJECTIVE: To briefly review strategies aimed at the development of rotavirus and HPV vaccines, with emphasis on the current status of studies assessing the safety, reactogenicity, immunogenicity and efficacy of recently developed vaccines. SOURCES OF DATA: This review focuses on articles published from 1996 to 2006, mainly those from the last five years, with special emphasis on data obtained from recently completed studies involving a new live attenuated human rotavirus vaccine and a virus-like particle (HPV) vaccine. SUMMARY OF THE FINDINGS: Strategies for developing rotavirus vaccines ranged from Jennerian approaches to the new human-derived rotavirus vaccine. Currently, two rotavirus vaccines are recognized as both efficacious and safe: a pentavalent human-bovine reassortant vaccine and a vaccine derived from an attenuated rotavirus of human origin. The second of these has been evaluated in more than 70,000 infants all over the world. Prophylactic vaccines against HPV have been tested in more than 25,000 young individuals around the world. Results from phase II and III clinical studies indicate that such vaccines against the most common types of HPV, those linked to both genital warts and 70% of cervical cancers, are safe and highly efficacious. CONCLUSIONS: A future rotavirus immunization program covering 60 to 80% of infants worldwide is likely to reduce by at least 50% the number of rotavirus-associated hospitalizations and deaths. It is also reasonable to expect that implementation of HPV prophylactic vaccines will reduce the burden of the HPV-related diseases that presently impact millions of people around the world. (+info)
Rotavirus serotype G9 is associated with more-severe disease in Latin America.
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The association between rotavirus serotypes and severity is not well established. Analysis of a clinical trial conducted in Latin America points at more-severe disease associated with serotype G9. Thus, demonstration of efficacy against G9 will be an important asset of any rotavirus vaccine to be introduced into a Latin American country or any country where G9 has been shown to be prevalent. (+info)
Safety, efficacy, and immunogenicity of 2 doses of bovine-human (UK) and rhesus-rhesus-human rotavirus reassortant tetravalent vaccines in Finnish children.
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BACKGROUND: Live oral rhesus-rhesus-human rotavirus reassortant tetravalent (RRV-TV) vaccine was efficacious against rotavirus gastroenteritis but was withdrawn because of a rare association with intussusception. A corresponding tetravalent (types G1, G2, G3, and G4) reassortant vaccine based on bovine-human (UK) rotavirus reassortant tetravalent (BRV-TV) vaccine was developed concurrently. METHODS: Before the withdrawal of RRV-TV vaccine, parallel placebo-controlled trials of BRV-TV vaccine (observer blinded) versus RRV-TV vaccine (double blinded) with a 2 : 1 ratio of vaccine : placebo were conducted in Finland in a total of 510 infants. Two doses of study vaccine or placebo were administered at ages 3 and 5 months. RESULTS: The first dose of RRV-TV vaccine was followed by a significant excess rate of febrile reactions (36%), whereas the rate of fever after the administration of BRV-TV vaccine did not differ significantly from that in the placebo group. Neither vaccine induced diarrhea. A seroresponse was detected in 97% of BRV-TV vaccine recipients and 94% of RRV-TV vaccine recipients. Both vaccines were equally effective, with 68%-69% efficacy against any and 88%-100% efficacy against severe rotavirus gastroenteritis during the first epidemic season. CONCLUSIONS: BRV-TV vaccine is a promising new candidate rotavirus vaccine, with low reactogenicity and high efficacy. Two doses of BRV-TV or RRV-TV vaccine are sufficient for the induction of protection against severe rotavirus disease. (+info)
Rotavirus vaccination and intussusception: can we decrease temporally associated background cases of intussusception by restricting the vaccination schedule?
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OBJECTIVE: The first rotavirus vaccine that was licensed in the United States, RotaShield, could have prevented the enormous burden of rotavirus diarrhea in American children but left instead the unfortunate legacy that live oral rotavirus vaccines may be associated with a serious but rare adverse event: intussusception. Although large trials indicate that the next generation of rotavirus vaccines is not associated with this complication, many children likely will develop intussusception by chance alone in the 2-week window after immunization, raising concerns about whether these cases might be "caused" by the vaccine. Our objective for this study was to model and compare the number of temporally associated intussusception events that are expected by chance alone under 2 rotavirus vaccination strategies. METHODS: We used national vaccine coverage rates and age-specific incidence of intussusception by months to model the number of temporally associated cases of intussusception that are expected by chance alone for 2 potential vaccination strategies: a strict schedule, limiting immunization to children within 1 month of the designated age for each dose (ie, 60-89, 120-149, and 180-209 days for doses 1, 2, and 3, respectively) versus a free schedule whereby infants are immunized whenever they appear for their routine vaccines up to 1 year of age. RESULTS: The number of intussusception events during the 2-week postvaccination window was 24% lower for the strict versus the free schedule (138 vs 182, respectively). This reduction was attributable largely to the smaller number of infants who were immunized fully under the strict schedule (vaccine coverage for 3 doses, 67% vs 89%). The cumulative risk for intussusception's occurring by chance in the 2-week postvaccination window essentially was the same between schedules (4.59 vs 4.76 per 100000 doses). Most cases occurred after the second or third dose. CONCLUSIONS: Although an age-restricted vaccination schedule substantially reduced the number of intussusception events that were observed in the 2-week postvaccination window when compared with a schedule with fewer restrictions, this decrease was attributable to a lower rate of vaccine coverage rather than a safer schedule of vaccination. The risk for intussusception did not differ significantly between vaccination strategies. Public health policy and education messages for physicians and parents should be developed to anticipate intussusception events that will occur by chance alone but are temporally related to rotavirus vaccination. (+info)
Prevention of rotavirus gastroenteritis among infants and children. Recommendations of the Advisory Committee on Immunization Practices (ACIP).
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In February 2006, a live, oral, human-bovine reassortant rotavirus vaccine (RotaTeq) was licensed for use among U.S. infants. The Advisory Committee on Immunization Practices recommends routine vaccination of U.S. infants with 3 doses of this rotavirus vaccine administered orally at ages 2, 4, and 6 months. The first dose should be administered between ages 6-12 weeks. Subsequent doses should be administered at 4-10 week intervals, and all 3 doses should be administered by age 32 weeks. Rotavirus vaccine can be co-administered with other childhood vaccines. Rotavirus vaccine is contraindicated for infants with a serious allergic reaction to any vaccine component or to a previous dose of vaccine. (+info)
Immunogenicity of a plant-derived edible rotavirus subunit vaccine transformed over fifty generations.
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Major efforts have been put forth for the development of effective rotavirus vaccines including transgenic plant vaccines. Previous studies have reported that rotavirus VP7 maintains its neutralizing immunity when it is transformed into the potato genome. The present study was aimed at investigating the hereditary stability of VP7-transformed potatoes over fifty generations. The VP7 gene was stably transcribed and expressed in potato cells as detected by RT-PCR and Western blotting. Humeral and mucosal responses were successfully induced in BALB/c mice fed with the fiftieth generation transformed potato tubers. There were no significant differences in serum IgG and fecal IgA between the mice fed with the first and fiftieth generation potatoes (P>0.05). Profiles of cytokines such as IFN-gamma, IL-2, IL-4, IL-5 and TGF-beta in immunized mice showed a naive T-cells bias to Th1 and Th3 polarization. Moreover, specific CTL responses were also detected in C57BL/6 mice fed with transformed potatoes. This research represents a significant step towards the development of rotavirus vaccines derived from a transgenic plant that can be obtained by long-term and large-scale vegetative reproduction. To our knowledge, this is the first finding regarding vaccines derived from plants that can be propagated for many generations. (+info)
Rotavirus infection enhances lipopolysaccharide-induced intussusception in a mouse model.
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Unexpected reports of intussusception after vaccination with the live tetravalent rotavirus vaccine RotaShield resulted in voluntary withdrawal of the vaccine. Intussusception, a condition in which the intestine acutely invaginates upon itself, is the most common cause of intestinal obstruction in children. We report here the development of a mouse model to study rotavirus-induced intussusception. In this model, both homologous murine and heterologous simian rotavirus strains significantly enhanced the rate of lipopolysaccharide (LPS)-induced intussusception, and this enhancement was replication dependent, requiring rotavirus doses of greater than one 50% infectious dose. Rotavirus-induced intussusceptions did not have observable lymphoid lead points, despite the induction of intestinal lymphoid hyperplasia after rotavirus infection. Intussusceptions are also postulated to result from altered intestinal motility, but rotavirus infection had no effect on gastrointestinal transit. LPS-induced intussusception is associated with the induction of inflammatory mediators, and intussusception rates can be modified by inflammatory antagonists. We show that rotavirus infection significantly enhanced serum tumor necrosis factor alpha and gamma interferon cytokine levels after LPS treatment compared to uninfected mice. Together, these data suggest that rotavirus infection sensitized mice to the inflammatory effects of subsequent LPS treatment to enhance intussusception rates. (+info)
The epidemiology of paediatric intussusception in Singapore: 1997 to 2004.
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INTRODUCTION: The world's first rotavirus vaccine, Rotashield or RRV-TV, was registered in the US in 1998, but withdrawn within a year because of an observed association with intussusception (IS). Surveillance for IS has consequently become important in safety monitoring of new-generation rotavirus vaccines during development. Post-marketing surveillance is also important, and requires the availability of local baseline epidemiology data on IS. MATERIALS AND METHODS: An eight-year study of IS in children under 2 years of age in Singapore was performed by retrospective review of admissions to KK Women's and Children's Hospital, the main paediatric hospital, from 1997 to 2001, followed by prospective surveillance of all hospitals from 2001 to 2004, using the case definition of the Brighton Collaboration Intussusception Working Group. RESULTS: The average IS incidence was 60 per 100,000 in under-ones, and 32 per 100,000 in under-twos, with a downward trend between 1999 and 2004. Ninety-two per cent of subjects were aged below one year, with 51% aged 6 months to 11 months. The mean age at which IS occurred increased from 6.4 months to 12.5 months over the study period. The male-to-female ratio was 1.3:1. No trend in IS numbers was observed over different months of the year. CONCLUSION: IS in Singapore shows no seasonality, but has demonstrated a trend of decreasing incidence in recent years. While highest in the first year of life, the risk of IS is increasing in the second year of life. Males have a slightly higher risk. (+info)