BUSCADOR RECOLECTA

Study of immune correlates against malaria after vaccination with RTS,S/ASO1E: a comphrensive immunological arm of a Phase III double-blind, randomize, controlled multi-centre trial (MAL067)., Dades primàries associades a l'article publicat a NPJ Vaccines, vol. 5 [https://doi.org/10.1038/s41541-020-0192-7], The RTS,S/AS01E vaccine has shown consistent but partial vaccine efficacy in a pediatric phase 3 26 clinical trial using a 3-dose immunization schedule. A fourth dose 18 months after the primary 27 vaccination was shown to restore the waning efficacy. However, only total IgG against the 28 immunodominant malaria vaccine epitope has been analyzed following the booster. To better 29 characterize the magnitude, nature and longevity of the immune response to the booster, we 30 measured levels of total IgM, IgG and IgG1-4 subclasses against three constructs of the 31 circumsporozoite protein (CSP) and the hepatitis B surface antigen (HBsAg, also present in RTS,S) 32 by quantitative suspension array technology in 50 subjects in the phase 3 trial in Manhiça, 33 Mozambique. To explore the impact of vaccination on naturally acquired immune responses, we 34 measured antibodies to P. falciparum antigens not included in RTS,S. We found increased IgG, 35 IgG1, IgG3 and IgG4, but not IgG2 nor IgM, levels against vaccine antigens one month after the 4th 36 dose. Overall, antibody responses to the booster dose were lower than the initial peak 37 response to primary immunization and children had higher IgG and IgG1 levels than infants. 38 Higher anti-Rh5 IgG and IgG1-4 levels were detected after the booster dose, suggesting that RTS,S 39 partial protection could increase some blood stage antibody responses. Our work shows that the 40 response to the RTS,S/AS01E booster dose is different from the primary vaccine immune 41 response and highlights the dynamic changes in subclass antibody patterns upon the vaccine 42 booster and with acquisition of adaptive immunity to malaria.

Dades primàries associades a l'article publicat a EClinicalMedicine, vol. 32 [https://doi.org./10.1016/j.eclinm.2020.100720], The trial was conducted in the Pamplona metropolitan area (Navarra, Spain). Patients were enrolled between July 31, 2020 and September 11, 2020 and randomized in a 1:1 ratio to ivermectin (400 mcg/kg) single oral dose or placebo. Assessments on enrollment and at days 4, 7, 14, 21 and 28 post treatment included: general symptoms report, physical examination and adverse events. All patients were asked to complete a daily online diary of symptoms from day 1 to 28 post treatment. On enrollment, as well as on days 7 and 14 blood samples were obtained to assess full blood count, C reactive protein, procalcitonin, ferritin, creatinine phosphokinase, lactic dehydrogenase, troponin T, D dimer, IL-6, and renal function. Viral loads were calculated at enrollment and on days 4, 7, 14 and 21 post treatment based on a nasopharyngeal swab for SARS-CoV-2 PCR (for genes N and E). A semi-quantitative serology for IgG against SARS-CoV-2 was done on samples from all patients on day 21 post-treatment.