BUSCADOR RECOLECTA

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.

The emergence of new SARS-CoV-2 variants and the waning of immunity raise concerns about vaccine effectiveness and protection against COVID-19. While antibody response has been shown to correlate with the risk of infection with the original variant and earlier variants of concern, the effectiveness of antibody-mediated protection against Omicron and the factors associated with protection remain uncertain. We evaluated antibody responseAQ2s to SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from Wuhan and variants of concern by Luminex and their role in preventing breakthrough infections 1 year after a third dose of mRNA vaccination, in a cohort of health care workers followed since the pandemic onset in Spain (N = 393). Data were analyzed in relation to COVID-19 history, demographic factors, comorbidities, vaccine doses, brand, and adverse events. Higher levels of anti-S IgG and IgA to Wuhan, Delta, and Omicron were associated with protection against vaccine breakthroughs (IgG against Omicron S antigen HR, 0.06, 95%CI, 0.26–0.01). Previous SARS-CoV-2 infection was positively associated with antibody levels and protection against breakthroughs, and a longer time since last infection was associated with lower protection. In addition, priming with BNT162b2 followed by mRNA-1273 booster was associated with higher antibody responses than homologous mRNA-1273 vaccination. Data show that IgG and IgA induced by vaccines against the original strain or by hybrid immunization are valid correlates of protection against Omicron BA.1 despite immune escape and support the benefits of heterologous vaccination regimens to enhance antibodies and the prioritization of booster vaccination in individuals without recent infections.

Databases containing raw analytical data obtained in the SEROCOV-1 and SEROCOVAC studies and personal covariates used in the publication Moncunill G, Aguilar R, et al EBioMedicine. 2022 Jan 11;75:103805. doi: 10.1016/j.ebiom.2021.103805. Data correspond to antibody levels to SARS-CoV-2 and four seasonal coronaviruses, and the neutralization capacity of samples from 578 participants recruited from 28 March- 9 April 2020, and the follow-up visits after one, three, six, nine and twelve months. In months 9 and 12, data on vaccination status was collected and some participants had already received the 1st (N=64) or the 2nd doses (N=4). Month 12 follow-up mostly included participants who had a blood sample taken two weeks post 2nd dose. The analytical data is completed with participants' information on occupation, comorbidities, previous COVID19 diagnoses and other sociodemographic characteristics. The code was developed using R version 4.0.3.

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.