Biomedical subjects

Timo Vesikari

Publications and source records attributed to Timo Vesikari.

At least 19 recordsLinked to original sources

PubMed2007

Efficacy, immunogenicity, and safety of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine at the end of shelf life.

BACKGROUND: Rotavirus is the leading cause of dehydrating acute gastroenteritis in infants worldwide. Previous studies of a live pentavalent human-bovine reassortant rotavirus vaccine have shown it to be efficacious across a range of potencies. OBJECTIVE: Our goal was to evaluate the efficacy, immunogenicity, and safety of pentavalent rotavirus vaccine at the end of shelf life in healthy infants. PATIENTS AND METHODS: During 2002-2004, 1312 healthy infants approximately 6 to 12 weeks old from the United States (47%) and Finland (53%) were randomly assigned to receive 3 oral doses of vaccine (vaccine at approximately 1.1 x 10(7) infectious U per dose) or placebo approximately 4 to 10 weeks apart. Infants were to be followed for acute gastroenteritis through 1 rotavirus season after vaccination and for adverse events postvaccination. RESULTS: Three doses of pentavalent rotavirus vaccine at the end of shelf life demonstrated efficacy against rotavirus gastroenteritis caused by human G-serotypes included in the vaccine (G1-G4). Efficacy against severe rotavirus gastroenteritis was 100%, and efficacy against any rotavirus gastroenteritis regardless of severity was 72.5%. A threefold rise in G1 serum neutralizing was observed in 57% and in anti-rotavirus immunoglobulin A in 96% of pentavalent rotavirus vaccine recipients. No statistically significant increase in vomiting, diarrhea, or irritability was observed among pentavalent rotavirus vaccine recipients compared with placebo recipients within the 7-day period from each dose. A statistically significant increase in fevers (> or = 100.5 degrees F, rectal equivalent) was observed among pentavalent rotavirus vaccine recipients compared with placebo recipients after dose 1. CONCLUSIONS: This pentavalent human-bovine rotavirus vaccine was generally well tolerated, efficacious, and immunogenic at the end of shelf life.

Acute Disease↗

PubMed2006

Safety, efficacy, and immunogenicity of 2 doses of bovine-human (UK) and rhesus-rhesus-human rotavirus reassortant tetravalent vaccines in Finnish children.

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.

Animals↗

PubMed2006

Effects of the potency and composition of the multivalent human-bovine (WC3) reassortant rotavirus vaccine on efficacy, safety and immunogenicity in healthy infants.

BACKGROUND: Rotavirus gastroenteritis, which causes substantial infant mortality and morbidity worldwide, is a vaccine-preventable disease. The purpose of this study was to evaluate different compositions and potencies (vaccine virus titers) of a live multivalent human-bovine (WC3) reassortant rotavirus vaccine in order to select the potency and composition of the vaccine for further development. METHODS: The efficacy, safety, and immunogenicity of a G1, G2, G3, G4, and P1A pentavalent composition at three different potencies, a G1, G2, G3, G4 quadrivalent composition, and a P1A monovalent composition of an oral human-bovine (WC3) reassortant rotavirus vaccine were compared in a blinded, placebo-controlled trial conducted between 1998 and 2001 enrolling 1,946 healthy Finnish infants 2-8 months of age. RESULTS: All potencies of the pentavalent and quadrivalent vaccines were efficacious (58-74%) against wild-type rotavirus gastroenteritis of any severity and 100% protective against severe rotavirus disease caused by vaccine G-serotypes through the first rotavirus season post-vaccination. The monovalent P1A vaccine was 53% efficacious against moderate-and-severe rotavirus gastroenteritis. Protection against rotavirus gastroenteritis of any severity was demonstrated through two and three rotavirus seasons for all vaccine compositions. After the third dose, the percentage of infants with >or=3-fold rise in baseline serum neutralizing antibody titers against G1 ranged from 62% to 86% for recipients of the pentavalent vaccine, depending on the potency. The incidence of fever, irritability, vomiting, and diarrhea did not significantly differ between vaccine and placebo groups. A 7-month-old male developed intussusception 9 days after the first dose of the low-potency pentavalent vaccine. CONCLUSIONS: Based on the results of this trial, a pentavalent composition (G1, G2, G3, G4, and P1A) of human-bovine (WC3) reassortant rotavirus vaccine with a potency similar to that of the middle-potency pentavalent vaccine ( approximately 8 x 10(6) plaque-forming units/dose) was selected for further development.

Animals↗

PubMed2006

Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis.

BACKGROUND: The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial. METHODS: We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients). RESULTS: The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78). CONCLUSIONS: Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.)

Administration, Oral↗

PubMed2006

Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine.

BACKGROUND: Rotavirus is a leading cause of childhood gastroenteritis and death worldwide. METHODS: We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive three oral doses of live pentavalent human-bovine (WC3 strain) reassortant rotavirus vaccine containing human serotypes G1, G2, G3, G4, and P[8] or placebo at 4-to-10-week intervals in a blinded fashion. Active surveillance was used to identify subjects with serious adverse and other events. RESULTS: The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events. Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose (relative risk, 1.6; 95 percent confidence interval, 0.4 to 6.4). The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent (95 percent confidence interval, 91.2 to 96.6 percent). In a nested substudy, efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent (95 percent confidence interval, 73.9 to 92.5 percent). CONCLUSIONS: This vaccine was efficacious in preventing rotavirus gastroenteritis, decreasing severe disease and health care contacts. The risk of intussusception was similar in vaccine and placebo recipients. (ClinicalTrials.gov number, NCT00090233.)

Administration, Oral↗

PubMed2006

Clinical trials of rotavirus vaccines in Europe.

Clinical trials of a live oral candidate rotavirus vaccine were started in 1982 and soon demonstrated that severe rotavirus disease can be prevented by vaccination. The first bovine candidate vaccine was withdrawn because of inconsistent efficacy, and studies of a rhesus rotavirus vaccine were initiated. A field trial of rhesus-human reassortant tetravalent rotavirus vaccine in Finland was pivotal for the licensure of this vaccine (RotaShield) in the United States in 1998. However, this vaccine was withdrawn in 1999 because of association with intussusception. Safety therefore became a major issue in the development of new candidate rotavirus vaccines. A pentavalent bovine-human reassortant rotavirus vaccine (RotaTeq) showed about 70% efficacy against any rotavirus disease and 100% efficacy against severe disease in Finland, according to the Clark scale. A large, multinational safety trial indicated no association of this vaccine with intussusception, and its licensure is under review in the EU. An attenuated human rotavirus vaccine (RIX4414; Rotarix) was developed from G1 rotavirus strain 89-12. A trial in Finland showed efficacy comparable with that of RotaShield, and a larger trial is under way in several European countries. In the first epidemic season, vaccine efficacy was 73% against any and 90% against severe rotavirus (mostly G1) gastroenteritis, according to the Vesikari scale. A large scale safety trial, conducted in Latin America plus Finland, indicated no increased risk of intussusception among recipients of Rotarix compared with placebo. The licensure of Rotarix is in process in the European Union.

Clinical Trials as Topic↗

PubMed2006

Burden of rotavirus disease in European Union countries.

Two new rotavirus vaccines are expected to be introduced in the European Union (EU) in coming years. A human rotavirus vaccine has already been licensed in several countries worldwide, and a pentavalent bovine vaccine has been submitted for licensure in the United States and the EU. Few data exist on the burden of rotavirus disease and its associated costs within the EU. To estimate the burden of rotavirus disease in the EU, we adapted a model based on the approach developed by the Centers for Disease Control and Prevention to the European situation and applied it to recent population and mortality data from European countries. Country-specific estimates were added to obtain a global estimate of rotavirus episodes treated at home, clinic visits, hospitalization and death. We estimate that 3.6 million episodes of rotavirus disease occur annually among the 23.6 million children younger than 5 years of age in the EU. Every year, rotavirus accounts for 231 deaths, >87,000 hospitalizations and almost 700,000 outpatient visits. Rotavirus disease constitutes a large public health burden in the EU. Except for deaths, the burden of disease is not dissimilar to that in the developing world. Country-specific studies are required to more accurately understand the burden of disease caused by rotavirus. With the introduction of new rotavirus vaccines in sight, rotavirus gastroenteritis may be regarded as the single most frequent vaccine-preventable disease among children in the EU.

Child, Preschool↗

PubMed2006

Rotavirus types in Europe and their significance for vaccination.

The degree of diversity of cocirculating human rotavirus wild-type strains is high. This article reviews the occurrence and frequency of rotavirus types in European children younger than 5 years of age during the past 10-15 years. To enable greater understanding of the overall epidemiologic situation, rotavirus types found in animals in Europe are described. In addition, rotavirus types occurring in children outside Europe are considered. Taken together, these data provide an essential background to the development of rotavirus vaccines. The different concepts of immunization with the 2 main rotavirus candidate vaccines are briefly discussed, and their potential impact on the epidemiology of cocirculating rotavirus wild-type viruses is considered. A case is made for comprehensive surveillance of cocirculating human rotavirus types in Europe after the implementation of rotavirus vaccination.

Age Distribution↗

PubMed2006

Neonatal administration of rhesus rotavirus tetravalent vaccine.

BACKGROUND AND AIMS: Administration of the first dose of rhesus rotavirus-based tetravalent (RRV-TV) vaccine is followed by a transient febrile reaction at 3-4 days postvaccination in about one-third of vaccinees. We hypothesized that giving the first dose of RRV-TV vaccine during the neonatal period might reduce the reactogenicity of RRV-TV vaccine without compromising the utilization of the vaccine. METHODS: A double blind placebo-controlled safety and immunogenicity trial of 90 infants who received RRV-TV vaccine at 0-4-6, 0-2-4 or 2-4-6 months of age was conducted. Reactions were evaluated for 1 week after each vaccination and, in addition, serum specimens were collected before vaccination and at 5 and 7 months of age. RESULTS: Febrile reactions were not observed in 62 infants receiving the first dose of RRV-TV vaccine during the neonatal period. Five of the 28 (18%) infants receiving the first dose at 2 months were febrile on 1 or more days, whereas none of the 30 infants who had received a neonatal dose developed a fever when vaccinated again at 2 months of age. An enzyme-linked immunosorbent assay IgA antibody response after 3 doses was observed significantly less frequently (77%) in infants who had received a neonatal dose, a second dose at 2 months of age, and a third dose at 4 months of age compared with those who received their first dose at 2 months and a second dose at 4 months (100%, P < 0.02). Also, the frequency of a neutralizing antibody response to RRV and human rotavirus serotypes G1-4 tended to be lower in the group that had received the vaccine at 0-2-4 months compared with those who received it at 2-4-6 months. When the 2 tests were combined, the frequency of a seroresponse following the 0-2-4 month schedule (94%) was comparable with that following the 2-4-6 month schedule (100%). CONCLUSION: Infants who received the first dose of RRV-TV vaccine during the neonatal period did not develop a febrile reaction. The immune response in a 3-dose schedule initiated in the neonatal period is somewhat dampened but still acceptable. Neonatal immunization might also reduce the very small risk of intussusception, which has been associated with administration of RRV-TV vaccine to older infants.

Administration, Oral↗

PubMed2006

A randomized, double-blind study of the safety, transmissibility and phenotypic and genotypic stability of cold-adapted influenza virus vaccine.

BACKGROUND: Live attenuated influenza vaccine (LAIV; FluMist) is a trivalent vaccine containing cold-adapted influenza vaccine viruses that infect and replicate in cells lining the nasopharynx to induce immunity. Recovery of viruses (shedding) is measured by culture of nasal specimens. Shedding of vaccine viruses is not equated with transmission because transmission requires more virus than is detected in many nasal swabs. Previous studies with LAIV did not detect transmission to close contacts. The primary objective of this study was to estimate the probability of transmission to placebo contacts in a day care setting. METHODS: One hundred ninety-seven healthy children aged 9 to 36 months attending day care were randomized to receive vaccine or placebo. Postvaccination viral shedding, safety, genotype and phenotype of shed viruses and probability of transmission were assessed. RESULTS: Eighty percent of 98 vaccine recipients shed at least one vaccine strain. No clinically significant differences in solicited adverse events attributable to vaccine occurred; safety profiles were similar in both groups. Vaccine virus isolates retained their phenotypic characteristics (cold adaptation and temperature sensitivity) and did not revert at nucleotides known to confer an attenuating phenotype. There was one confirmed transmission of a vaccine strain to a single placebo recipient. According to the Reed-Frost model, the calculated probability of transmission to a child after contact with a single vaccinated child was 0.58% (95% confidence interval, 0-1.7%). There was no increased reactogenicity or other safety concerns in the recipient child. CONCLUSIONS: Young children in a day care setting had a high rate of shedding and a low rate of transmission. No clinically significant illness occurred among children who received vaccine or placebo or in the child to whom the vaccine virus was transmitted.

Child Day Care Centers↗

PubMed2006

Safety, efficacy, and effectiveness of cold-adapted influenza vaccine-trivalent against community-acquired, culture-confirmed influenza in young children attending day care.

OBJECTIVE: The goal was to evaluate the safety, tolerability, and efficacy of an investigational, refrigerator-stable formulation of live attenuated influenza vaccine (cold-adapted influenza vaccine-trivalent) against culture-confirmed influenza, acute otitis media, and effectiveness outcomes in young children in day care over 2 consecutive influenza seasons. METHODS: Children 6 to <36 months of age who were attending day care were assigned randomly in year 1 to receive 2 doses of vaccine or placebo intranasally, 35 +/- 7 days apart. In year 2, subjects received 1 dose of the same treatment as in year 1. RESULTS: A total of 1616 subjects (vaccine: 951 subjects; placebo: 665 subjects) in year 1 and 1090 subjects (vaccine: 640 subjects; placebo: 450 subjects) in year 2 were able to be evaluated for efficacy. The mean age at first vaccination was 23.4 +/- 7.9 months. In year 1, the overall efficacy of the vaccine against influenza subtypes similar to the vaccine was 85.4%; efficacy was 91.8% against A/H1N1 and 72.6% against B. In year 2, the overall efficacy was 88.7%; efficacy was 90.0% against H1N1, 90.3% against A/H3N2, and 81.7% against B. Efficacy against all episodes of acute otitis media associated with culture-confirmed influenza was 90.6% in year 1 and 97.0% in year 2. Runny nose or nasal discharge after dose 1 in year 1 was the only reactogenicity event that was significantly more frequent with cold-adapted influenza vaccine-trivalent (82.3%) than placebo (75.4%). CONCLUSIONS: Cold-adapted influenza vaccine-trivalent was well tolerated and effective in preventing culture-confirmed influenza illness in children as young as 6 months of age who attended day care.

Acute Disease↗

PubMed2006

[Not Available].

Explore the source record for details and available documents.

Editorial↗

PubMed2005

A DNA HIV-1 vaccine based on a fusion gene expressing non-structural and structural genes of consensus sequence of the A-C subtypes and the ancestor sequence of the F-H subtypes. Preclinical and clinical studies.

A potent DNA vaccine against HIV, combining a vector that takes advantage of the segregation and compartmentalization effect of bovine papilloma virus E2 protein with MultiHIV insert, expressing a fusion gene coding for the non-structural and structural proteins was developed and tested for immunogenicity in mice and humans.

AIDS Vaccines↗

PubMed2005

A hexavalent human rotavirus-bovine rotavirus (UK) reassortant vaccine designed for use in developing countries and delivered in a schedule with the potential to eliminate the risk of intussusception.

There is an urgent need for a rotavirus vaccine, because up to 592,000 infants and young children <5 years old die each year from rotavirus diarrhea, predominantly in the developing countries. We have developed a tetravalent human-bovine rotavirus (UK) reassortant vaccine with VP7 (G) specificity for serotypes 1, 2, 3, and 4, which has been shown to be safe, immunogenic, and effective in preventing severe rotavirus diarrhea. However, because of the emergence of VP7 (G) serotype 9 as an epidemiologically important serotype and the importance of VP7 (G) serotype 8 in focal areas, we are planning to add human-bovine (UK) reassortants with G8 and G9 specificity to the tetravalent vaccine, thereby formulating a "designed" hexavalent vaccine for universal use. In addition, we propose that the vaccine be administered orally in a 2-dose schedule, with the first dose given at 0-4 weeks of age and the second dose given at 4-8 weeks of age, when infants are relatively refractory to developing intussusception, thereby avoiding the age period when naturally occurring intussusception is most prevalent (i.e., ages 3-4 months through age 9 months). In this way, there may be the potential to eliminate or at least significantly decrease the risk of intussusception associated with rotavirus vaccination.

Administration, Oral↗

PubMed2005

Genetic diversity of JC virus in the Saami and the Finns: implications for their population history.

The JC virus (JCV) genotyping method was used to gain insights into the population history of the Saami and the Finns, both speaking Finno-Ugric languages and living in close geographic proximity. Urine samples from Saami and Finns, collected in northern and southern Finland, respectively, were used to amplify a 610-bp JCV-DNA region containing abundant type-specific mutations. Based on restriction site polymorphisms in the amplified fragments, we classified JCV isolates into one of the three superclusters of JCV, type A, B, or C. All 15 Saami isolates analyzed and 41 of 43 Finnish isolates analyzed were classified as type A, the European type, and two samples from Finns were classified as type B, the African/Asian type. We then amplified and sequenced a 583-bp JCV-DNA region from the type A isolates of Saami and Finns. According to type-determining nucleotides within the region, we classified type A isolates into EU-a1, -a2, or -b. Most type A isolates from Saami were classified as EU-a1, while type A isolates from Finns were distributed among EU-a1, EU-a2, and EU-b. This trend in the JCV-genotype distribution was statistically significant. On a phylogenetic tree based on complete sequences, most of the type A isolates from Saami were clustered in a single clade within EU-a1, while those from Finns were distributed throughout EU-a1, EU-a2, and EU-b. These findings are discussed in the context of the population history of the Saami and the Finns. This study provides new complete JCV DNA sequences derived from populations of anthropological interest.

Adult↗

PubMed2005

A six-fold gradient in the incidence of type 1 diabetes at the eastern border of Finland.

OBJECTIVE: Type 1 diabetes results from gene-environment interactions in subjects with genetic susceptibility to the disease. We assessed the contribution of environmental and genetic factors to type 1 diabetes by comparing the incidence in two neighboring populations living in conspicuously different socioeconomic circumstances. RESEARCH DESIGN AND METHODS: We compared the incidence over a 10-year period (1990-99) in children younger than 15 years of age living in the Karelian Republic of Russia and in Finland. The frequency of susceptible and protective human leukocyte antigen (HLA)-DQ alleles was analyzed in 400 non-diabetic schoolchildren from Russian Karelia and 1000 Finnish subjects. RESULTS: The average annual age-adjusted incidence of type 1 diabetes was lower in Russian Karelia than in Finland: 7.4 per 100000 (95% confidence interval 3.5-11.3) versus 41.4 per 100000 (37.3-45.5), while there were no differences in the frequency of the HLA DQ genotypes predisposing to type 1 diabetes in the background populations. The incidence rate did not differ significantly between different ethnic groups in Russian Karelia (Finns/Karelians, Russians, others). CONCLUSIONS: There is a close to six-fold gradient in the incidence of type 1 diabetes between Russian Karelia and Finland, although the predisposing HLA DQ genotypes are equally frequent in the two populations. This suggests that environmental factors contribute to this steep difference in the incidence rate between these adjacent regions.

Adolescent↗

PubMed2005

Viral etiology and incidence of acute gastroenteritis in young children attending day-care centers.

BACKGROUND: The purpose of the study was to investigate the frequency, morbidity and cause of acute gastroenteritis in children attending day-care centers in Denmark. METHODS: Children with acute diarrhea (> or =2 consecutive loose stools in 24 hours, with duration of < or =7 days), recruited from 19 day-care centers, were included. Gastroenteritis viruses, group A rotavirus, sapoviruses, noroviruses and astroviruses were detected with reverse transcription-polymerase chain reaction assays. In addition, stool specimens were cultured for bacterial pathogens. Children who were brought to the clinic with acute diarrhea underwent a medical evaluation, including an estimation of dehydration. RESULTS: Two hundred seven children (median age, 20.1 months; range, 9-44 months) were enrolled. During the 6-month study period, 98 diarrheal episodes in 95 children were reported. Of these, 48 were reported retrospectively in telephone interviews. The incidence of acute diarrheal episodes was 0.08 episode per child per month. A viral etiologic agent was identified in 69% of cases. Rotaviruses were identified in 17 cases (40%), sapoviruses in 8 (19%) and astroviruses in 3 (7%). One patient had a coinfection with rotavirus and astrovirus. Campylobacter jejuni was detected in 2 patients and Clostridium difficile was found in 5 patients, all coinfected with a virus. In clinical assessments, 9 patients (18%) showed signs of dehydration and were given oral rehydration solution; 6 of these were hospitalized. CONCLUSIONS: Acute diarrhea among children attending day-care centers was common in wintertime. Rotaviruses were, expectedly, the most common causative agents, but sapoviruses were second to rotaviruses as etiologic agents in this population.

Acute Disease↗

PubMed2004

Efficacy of RIX4414 live attenuated human rotavirus vaccine in Finnish infants.

BACKGROUND: Rotavirus gastroenteritis, a major cause of mortality and morbidity worldwide, is a vaccine-preventable disease. New safe and effective candidate rotavirus vaccines are needed to replace the withdrawn rhesus rotavirus-based oral vaccine. METHODS: We evaluated a monovalent human rotavirus vaccine, serotype G1, strain RIX4414, for efficacy, immunogenicity and safety in a randomized, double blind, placebo-controlled trial in Finland. We randomly allocated 405 healthy infants to receive 2 doses of vaccine or placebo (ratio 2:1) at approximately 2 and 4 months of age. The infants were followed during 2 rotavirus epidemic seasons (2000-2002) for acute gastroenteritis. Rotaviruses in diarrheal stool samples were primarily detected by enzyme-linked immunosorbent assay and confirmed and G-typed by reverse transciption-polymerase chain reaction. RESULTS: The vaccine was well-tolerated. No vaccine-related serious adverse events were observed during the study period. Rotavirus IgA (enzyme-linked immunosorbent assay) seroconversion rate was 80% after 2 doses. Thirty-eight cases of rotavirus gastroenteritis were detected during the entire follow-up period; 35 of these were of the G1 type. RIX4414 vaccine significantly decreased the occurrence of any rotavirus compared with placebo. Efficacy during the first rotavirus epidemic season was 73% [95% confidence interval (95% CI), 27-91%] and 90% (95% CI 10-100%) against any and severe rotavirus gastroenteritis, respectively, and during the entire follow-up period 72% (95% CI 42-87%) against any and 85% (95% CI 42-97%) against severe rotavirus gastroenteritis (P < 0.05 for all comparisons). CONCLUSIONS: RIX4414 strain of G1 human rotavirus vaccine was well-tolerated, immunogenic and efficacious in infants against rotavirus gastroenteritis during a 2-year period. To further increase vaccine "take" and efficacy, a higher dose of this vaccine may be considered for future efficacy trials.

Administration, Oral↗