Specific neutralizing response in plasma from convalescent patients of Ebola Virus Disease against the West Africa Makona variant of Ebola virus.

Luczkowiak, Joanna; Arribas, José R; Gómez, Sara; Jiménez-Yuste, Víctor; de la Calle, Fernando; Viejo, Aurora; Delgado, Rafael

BACKGROUND The current outbreak of Ebola Virus Disease in West Africa is caused by a new variant of Ebola virus (EBOV) named Makona 2014, whose sequence differs 3% from isolates from Central Africa such as Mayinga 1976 EBOV. The specificity and kinetics of the neutralizing antibody response induced by the circulating Makona EBOV has not been thoroughly studied. METHODS We have used a lentiviral EBOV-glycoprotein (GP)-pseudotyped infection assay to measure Makona-GP and Mayinga-GP specific neutralizing activity of plasma from three convalescent Ebola Virus Disease patients from the current EBOV outbreak at 2, 3, 4 and 9 months post-infection. Total anti-EBOV GP IgG was measured by a commercial ELISA assay. FINDINGS In convalescent Ebola Virus Disease patients, Makona-GP-specific neutralizing titers increased from 2 months (mean IC50 1/59), 3 months (IC50 1/212), 4 months (IC50 1/239) and up to 9 months (IC50 1/268) post-infection. Neutralizing activity of plasma from the three convalescent Ebola Virus Disease patients was more vigorous against the current Makona-GP pseudotyped EBOV variant than against Mayinga-GP pseudotyped EBOV and this difference was observed at each time point tested: Mayinga vs Makona mean IC50 fold=4.92 at 2 months post-infection, 2.89 fold at 3 months post-infection, 2.23 at 4 months post-infection and 2.98 at 9 months post-infection (all differences p<0.01). Total level of IgG against EBOV-GP did not evolve significantly during the follow up. DISCUSSION In convalescent Ebola Virus Disease patients, EBOV-GP specific neutralizing activity increases over time, at least up to 9 months post-infection, which suggests that active affinity maturation of antibodies takes place long after clinical recovery. EBOV-GP specific neutralizing response is significantly higher against Makona EBOV circulating in West Africa than against the variants included in the currently approved vaccines. Correlates of protection for EBOV vaccines have not been completely established and the relevance of a lower neutralizing activity in convalescent plasma from the current outbreak against one of the EBOV-GPs contained in the vaccines in terms of its potential efficacy does not necessarily preclude its efficacy. However, this observation highlights the concern regarding the natural diversity of EBOV and its subsequent challenge for diagnosis, therapy and vaccine design. EBOV-GP neutralizing activity varies considerably over time in convalescent Ebola Virus Disease patients. Titering of convalescent blood products would be desirable to standardize and evaluate their potential therapeutic value.