Reactogenicity and immunogenicity of inactivated poliovirus vaccine produced from Sabin strains: a phase I Trial in healthy adults in Cuba.

BACKGROUND: To ensure that developing countries have the option to produce inactivated poliovirus vaccine (IPV), the Global Polio Eradication Initiative has promoted the development of an IPV using Sabin poliovirus strains (Sabin IPV). This trial assessed the reactogenicity and immunogenicity of Sabin IPV and adjuvanted Sabin IPV in healthy adults in Cuba. METHODS: This is a randomized, controlled phase I trial, enrolling 60 healthy (previously vaccinated) male human volunteers, aged 19-23 years to receive one dose of either Sabin IPV (20:32:64 DU/dose), adjuvanted Sabin IPV (10:16:32 DU/dose), or conventional Salk IPV (40:8:32 DU/dose). The primary endpoint for reactogenicity relied on monitoring of adverse events. The secondary endpoint measured boosting immune responses (i.e. seroconversion or 4-fold rise) of poliovirus antibody, assessed by neutralization assays. RESULTS: Sixty subjects fulfilled the study requirements. No serious adverse events reported were attributed to trial interventions during the 6-month follow-up period. Twenty-eight days after vaccination, boosting immune responses against poliovirus types 1-3 were between 90% and 100% in all vaccination groups. There was a more than 6-fold increase in median antibody titers between pre- and post-vaccination titers in all vaccination groups. DISCUSSION: Both Sabin IPV and adjuvanted Sabin IPV were well tolerated and immunogenic against all poliovirus serotypes. This result suggests that the aluminum adjuvant may allow a 50% (or higher) dose reduction.

Priming after a fractional dose of inactivated poliovirus vaccine.

BACKGROUND: To reduce the costs of maintaining a poliovirus immunization base in low-income areas, we assessed the extent of priming immune responses after the administration of inactivated poliovirus vaccine (IPV). METHODS: We compared the immunogenicity and reactogenicity of a fractional dose of IPV (one fifth of a full dose) administered intradermally with a full dose administered intramuscularly in Cuban infants at the ages of 4 and 8 months. Blood was collected from infants at the ages of 4 months, 8 months, 8 months 7 days, and 8 months 30 days to assess single-dose seroconversion, single-dose priming of immune responses, and two-dose seroconversion. Specimens were tested with a neutralization assay. RESULTS: A total of 320 infants underwent randomization, and 310 infants (96.9%) fulfilled the study requirements. In the group receiving the first fractional dose of IPV, seroconversion to poliovirus types 1, 2, and 3 occurred in 16.6%, 47.1%, and 14.7% of participants, respectively, as compared with 46.6%, 62.8%, and 32.0% in the group receiving the first full dose of IPV (P<0.008 for all comparisons). A priming immune response to poliovirus types 1, 2, and 3 occurred in 90.8%, 94.0%, and 89.6% of participants, respectively, in the group receiving the fractional dose as compared with 97.6%, 98.3%, and 98.1% in the group receiving the full dose (P=0.01 for the comparison with type 3). After the administration of the second dose of IPV in the group receiving fractional doses, cumulative two-dose seroconversion to poliovirus types 1, 2, and 3 occurred in 93.6%, 98.1%, and 93.0% of participants, respectively, as compared with 100.0%, 100.0%, and 99.4% in the group receiving the full dose (P<0.006 for the comparisons of types 1 and 3). The group receiving intradermal injections had the greatest number of adverse events, most of which were minor in intensity and none of which had serious consequences. CONCLUSIONS: This evaluation shows that vaccinating infants with a single fractional dose of IPV can induce priming and seroconversion in more than 90% of immunized infants. (Funded by the World Health Organization and the Pan American Health Organization; Australian New Zealand Clinical Trials Registry number, ACTRN12610001046099.).

Randomized controlled clinical trial of fractional doses of inactivated poliovirus vaccine administered intradermally by needle-free device in Cuba.

BACKGROUND: As part of an evaluation of strategies to make inactivated poliovirus vaccine (IPV) affordable for developing countries, we conducted a clinical trial of fractional doses of IPV in Cuba. METHODS: We compared the immunogenicity and reactogenicity of fractional-dose IPV (0.1 mL, or 1/5 of a full dose) given intradermally using a needle-free jet injector device compared with full doses given intramuscularly. Subjects were randomized at birth to receive IPV at 6, 10, and 14 weeks. RESULTS: A total of 471 subjects were randomized to the 2 study groups, and 364 subjects fulfilled the study requirements. No significant differences at baseline were detected. Thirty days after completing the 3-dose schedule of IPV, 52.9%, 85.0%, and 69.0% of subjects in the fractional-dose IPV arm seroconverted for poliovirus types 1, 2, and 3, respectively, whereas 89.3%, 95.5%, and 98.9% of subjects in the full-dose IPV arm seroconverted for poliovirus types 1, 2, and 3, respectively (all comparisons, P < .001). The median titers of each poliovirus serotype were significantly lower in the intradermal arm than in the intramuscular arm (P < .001). Only minor local adverse effects and no moderate or serious adverse events were reported. CONCLUSIONS: This large-scale evaluation demonstrates the feasibility of fractional doses of IPV given intradermally as an antigen-sparing strategy but also shows that IPV given to infants at 6, 10, and 14 weeks of age results in suboptimal immunogenicity (especially for the fractional-dose arm).

Exposición humana a rabia animal en Puerto Rico, 1980-1983 / Human exposure to animal rabies in Puerto Rico, 1980-1983

El manejo apropiado de las heridas, y la administración correcta de profilaxis antirrábica son mandatorios para evitar un desenlace mortal en las personas que han sufrido mordeduras por animales. Una alta proporción de mangostas(Herpestes auropunctatus) capturadas en Puerto Rico alberga el virus de rabia. De 1980 a 1983 se encontraron mangostas con rabia en todas las regiones de la isla, y durante todas las estaciones del año. El hallazgo de rabia en perros y gatos ocurrió con mucho menor frecuencia que en las mangostas. Los roedores (ratas, ratones y hamsters) y lagomorfos (conejos y liebres) examinados en el laboratorio fueron todos negativos para rabia. La tasa general de tratamientos antirrábicos en Puerto Rico en 1983 fue 4.77 por cien mil habitantes y el costo de los agentes inmunológicos fue de $60,528. La tasa de tratamiento de varones fue mayor que la de mujeres (6.15 vs. 3.46 por cien mil habitantes). El manejo apropiado de mordeduras por animales se resume con el acróstico RATAS (R-abia, A-ntibióticos, T-étanos, AS-epsia). Para cada víctima de una mordedura hay que considerar la necesidad de profilaxis contra rabia; la necesidad de antibióticos para tratar heridas infectadas, sucias, o severas; la necesidad de inyectarle al paciente antitoxina o inmunoglobulina antitetánica; y la utilidad de limpiar la herida con jabón o desinfectantes