PubMed Health⌕ Search

Biomedical subjects

N Kanesa-Thasan

Publications and source records attributed to N Kanesa-Thasan.

7 recordsLinked to original sources
PubMed2003

Phase 1 studies of Walter Reed Army Institute of Research candidate attenuated dengue vaccines: selection of safe and immunogenic monovalent vaccines.

We describe the results of initial safety testing of 10 live-attenuated dengue virus (DENV) vaccine candidates modified by serial passage in primary dog kidney (PDK) cells at the Walter Reed Army Institute of Research. The Phase 1 studies, conducted in 65 volunteers, were designed to select an attenuated vaccine candidate for each DENV serotype. No recipient of the DENV candidate vaccines sustained serious injury or required treatment. Three vaccine candidates were associated with transient idiosyncratic reactions in one volunteer each, resulting in their withdrawal from further clinical development. Increasing PDK cell passage of DENV-1, DENV-2, and DENV-3 candidate vaccines increased attenuation for volunteers, yet also decreased infectivity and immunogenicity. This effect was less clear for DENV-4 candidate vaccines following 15 and 20 PDK cell passages. Only one passage level each of the tested DENV-2, -3, and -4 vaccine candidates was judged acceptably reactogenic and suitable for expanded clinical study. Subsequent studies with more recipients will further establish safety and immunogenicity of the four selected vaccine candidates: DENV-1 45AZ5 PDK 20, DENV-2 S16803 PDK 50, DENV-3 CH53489 PDK 20, and DENV-4 341750 PDK 20.

Adolescent↗
PubMed2003

Atypical antibody responses in dengue vaccine recipients.

Eight of 69 (12%) healthy adult volunteers vaccinated with monovalent live-attenuated dengue virus (DENV) vaccine candidates had atypical antibody responses, with depressed IgM:IgG antibody ratios and induction of high-titer hemagglutination-inhibiting and neutralizing (NT) antibodies to all four DENV serotypes. These features suggested flavivirus exposure prior to DENV vaccination, yet no volunteer had a history of previous flavivirus infection, flavivirus vaccination, or antibody to flaviviruses evident before DENV vaccination. Moreover, production of antibody to DENV by atypical responders (AR) was not accelerated compared with antibody responses in the 61 flavivirus-naive responders (NR). Further evaluation revealed no differences in sex, age, race, DENV vaccine candidate received, or clinical signs and symptoms following vaccination between AR and NR. However, viremia was delayed at the onset in AR compared with NR. A comparative panel of all AR and five randomly selected NR found flavivirus cross-reactive antibody after vaccination only in AR. Unexpectedly, six of eight AR had NT antibodies to yellow fever virus (YFV) > 1:10 before vaccination while NR had none (P = 0.04). The AR also universally demonstrated YFV NT antibody titers > or = 1:160 after DENV vaccination, whereas four of five NR failed to seroconvert (P = 0.02). Yellow fever virus priming broadens the antibody response to monovalent DENV vaccination. The effect of flavivirus priming on the clinical and immunologic response to tetravalent DENV vaccine remains to be determined.

Adolescent↗
PubMed2002

Short report: absence of protective neutralizng antibodies to West Nile virus in subjects following vaccination with Japanese encephalitis or dengue vaccines.

Protection of individuals against West Nile (WN) encephalitis is an emerging concern in the United States and Europe. We investigated whether immunization with licensed inactivated Japanese encephalitis (JE) vaccine or experimental live attenuated dengue vaccines resulted in induction of cross-neutralizing antibodies against WN virus. Protective neutralizing antibody titers to WN virus were not detected in any volunteer despite successful immunization to related flaviviruses. Vaccination against JE or dengue is unlikely to prevent WN virus infection but may still protect against disease.

Antibodies, Viral↗
PubMed2001

Haiti: absence of dengue hemorrhagic fever despite hyperendemic dengue virus transmission.

In 1994-1996, 185 strains of dengue (DEN) virus types 1, 2, and 4 were recovered from febrile United States and other United Nations military personnel in Haiti. We wondered whether risk factors for dengue hemorrhagic fever (DHF) existed and, if so, were DHF cases occurring among Haitian children. Dengue transmission rates were studied in 210 school children (6-13 years old) resident in Carrefour Borough, Port-au-Prince, Haiti. When sera were tested for plaque-reduction neutralizing antibodies to DEN 1-4 viruses, nearly 85% had antibodies to two or more DEN serotypes. The annual transmission rate was estimated at 30%, a rate observed in countries endemic for DHE Haitian DEN 2 isolates were genotype I, which are repeatedly associated with DHF cases in Southeast Asia and American regions. Despite positive virologic pre-conditions, DHF cases were not recorded by experienced Port-au-Prince pediatricians. These observations, which are reminiscent of those in Africa, provide further evidence of a dengue resistance gene in black populations.

Adolescent↗
PubMed1998

Induction of Japanese encephalitis virus-specific cytotoxic T lymphocytes in humans by poxvirus-based JE vaccine candidates.

Poxvirus-based recombinant Japanese encephalitis (JE) vaccine candidates, NYVAC-JEV and ALVAC-JEV, were examined for their ability to induce JE virus-specific cytotoxic T lymphocytes (CTLs) in a phase I clinical trial. These vaccine candidates encoded the JE virus premembrane (prM), envelope (E) and non-structural 1 (NS1) proteins. The volunteers received subcutaneous inoculations with each of these candidates on days 0 and 28, and blood was drawn 2 days before vaccination and on day 58. Anti-E and anti-NS1 antibodies were elicited in most vaccinees inoculated with NYVAC-JEV and in some vaccinees inoculated with ALVAC-JEV. Peripheral blood mononuclear cells (PBMCs) obtained from approximately one half of vaccines showed positive proliferation in response to stimulation with live JE virus. Cytotoxic assays demonstrated the presence of JE virus-specific CTLs in in vitro-stimulated PBMCs obtained from two NYVAC-JEV and two ALVAC-JEV vaccinees. Cell depletion tests using PBMCs from one NYVAC-JEV recipient indicated that the phenotype of CTLs was CD8+CD4-.

Adult↗
PubMed1995

Short report: hepatitis E infection in the Brazilian Amazon.

This is the first report of serologic evidence of hepatitis E infection in Brazil. During a community-based survey of healthy individuals, six of 97 gold miners in the Amazon region of Mato Grosso had antibody to the virus. The mining camps have poor sanitation with a great potential for fecal-oral transmission of disease. Since levels of hepatitis E antibodies may quickly wane, studies to directly measure the incidence of seroconversion are planned to determine the intensity of transmission in this area.

Adult↗