RESUMEN
We conducted a phase 1 trial of candidate malaria vaccine RTS,S/AS02A in western Kenya to determine its safety and immunogenicity in healthy adults in an area hyperendemic for malaria. Twenty adults were enrolled and received RTS,S/AS02A (50 microg of RTS,S in 0.5 mL of AS02A) by intramuscular injection on a 0-, 28-, and 178-day schedule. All 60 scheduled immunizations were given, and 18 of 20 volunteers completed the last study visit on day 210. The vaccine was safe and well-tolerated. There were no vaccine-related severe adverse events. The most common solicited adverse events associated with immunization were injection site pain and headache. The geometric mean concentration of antibodies to circumsporozoite protein was 1.9 microg/mL at baseline and it increased 2-4 weeks after each dose to 16, 17.8, and 36.6 microg/mL, respectively. These safety and immunogenicity data from adults in hyperendemic Kenya are comparable to data reported earlier from two trials in west African adults in hypo-endemic and meso-endemic areas of The Gambia. We conclude that in this small study, RTS,S/AS02A is safe and similarly immunogenic in malaria-exposed African adults of different ethnicity in different transmission settings.
Asunto(s)
Enfermedades Endémicas , Vacunas contra la Malaria/inmunología , Malaria/prevención & control , Proteínas Protozoarias/inmunología , Vacunas de ADN/inmunología , Adolescente , Adulto , Animales , Anticuerpos Antiprotozoarios/sangre , Anticuerpos Antivirales/sangre , Formación de Anticuerpos/inmunología , Combinación de Medicamentos , Epítopos de Linfocito T/inmunología , Femenino , Antígenos de Superficie de la Hepatitis B/inmunología , Humanos , Kenia/epidemiología , Lípido A/análogos & derivados , Lípido A/inmunología , Malaria/epidemiología , Vacunas contra la Malaria/efectos adversos , Vacunas contra la Malaria/normas , Masculino , Saponinas/inmunología , Factores de Tiempo , Vacunas de ADN/efectos adversos , Vacunas de ADN/normasRESUMEN
Severe anemia is one of the most lethal complications of Plasmodium falciparum malaria. Red blood cells (RBCs) from children with severe malarial anemia are deficient in complement regulatory proteins (CR1 and CD55). A case-control, age- and sex-matched study was carried out to determine whether these deficiencies are acquired or inherited and the relative contribution of these complement regulatory protein deficiencies, the immune complex level, and the parasite density to the development of severe malarial anemia. RBC CR1 and CD55 deficiencies resolved after treatment, suggesting that these changes were acquired. Using conditional logistic regression, a decline in CD55 (or CR1) (odds ratio [OR], 4.2; 95% confidence interval [CI], 2.1-8.1; P<.001) and an increase in immune complex level (OR, 2.6; 95% CI, 1.5-4.8; P=.001) were significantly associated with severe malarial anemia.