Our findings show that active placental P. falciparum infection detected at delivery is associated with an approximately 2-fold greater risk of malaria during early life, compared with noninfection. The fact that persons born to infected multigravidae rather than primigravidae appear to be at greater risk emphasizes the importance of preventing malaria in mothers of all gravidities.

Immunogenicity and safety of different adjuvants combined with a model antigen (HBsAg) were compared. Healthy HBV-naïve adults were randomized to receive HBs adjuvanted with alum or Adjuvant Systems AS01B, AS01E, AS03A or AS04 at Days 0 and 30. Different frequencies of HBs-specific CD4+ T cells 14days post dose 2 but similar polyfunctionality profiles were induced by the different adjuvants with frequencies significantly higher in the AS01B and AS01E groups than in the other groups. Antibody concentrations 30days post-dose 2 were significantly higher in AS01B, AS01E and AS03A than in other groups. Limited correlations were observed between HBs-specific CD4+ T cell and antibody responses. Injection site pain was the most common solicited local symptom and was more frequent in AS groups than in alum group. Different adjuvants formulated with the same antigen induced different adaptive immune responses and reactogenicity patterns in healthy naïve adults. The results summary for this study (GSK study number 112115 - NCT# NCT00805389) is available on the GSK Clinical Study Register and can be accessed at www.gsk-clinicalstudyregister.com.

There is an urgent need for vaccines to counter the COVID-19 pandemic due to infections with severe acute respiratory syndrome coronavirus (SARS-CoV-2). Evidence from convalescent sera and preclinical studies has identified the viral Spike (S) protein as a key antigenic target for protective immune responses. We have applied an mRNA-based technology platform, RNActive®, to develop CVnCoV which contains sequence optimized mRNA coding for a stabilized form of S protein encapsulated in lipid nanoparticles (LNP). Following demonstration of protective immune responses against SARS-CoV-2 in animal models we performed a dose-escalation phase 1 study in healthy 18-60 year-old volunteers.This interim analysis shows that two doses of CVnCoV ranging from 2 μg to 12 μg per dose, administered 28 days apart were safe. No vaccine-related serious adverse events were reported. There were dose-dependent increases in frequency and severity of solicited systemic adverse events, and to a lesser extent of local reactions, but the majority were mild or moderate and transient in duration. Immune responses when measured as IgG antibodies against S protein or its receptor-binding domain (RBD) by ELISA, and SARS-CoV-2-virus neutralizing antibodies measured by micro-neutralization, displayed dose-dependent increases. Median titers measured in these assays two weeks after the second 12 μg dose were comparable to the median titers observed in convalescent sera from COVID-19 patients. Seroconversion (defined as a 4-fold increase over baseline titer) of virus neutralizing antibodies two weeks after the second vaccination occurred in all participants who received 12 μg doses.Preliminary results in the subset of subjects who were enrolled with known SARS-CoV-2 seropositivity at baseline show that CVnCoV is also safe and well tolerated in this population, and is able to boost the pre-existing immune response even at low dose levels.Based on these results, the 12 μg dose is selected for further clinical investigation, including a phase 2b/3 study that will investigate the efficacy, safety, and immunogenicity of the candidate vaccine CVnCoV.

No abstract