Porgaviximab

The use of specific anti-Ebola virus therapy, especially monoclonal antibodies, has improved survival in patients with Ebola virus disease. We aimed to assess the effect of monoclonal antibodies on anti-Ebola virus antibody responses in survivors of the 2018-20 Ebola outbreak in the Democratic Republic of the Congo.

In this observational prospective cohort study, participants were enrolled at three Ebola survivor clinics in Beni, Mangina, and Butembo (Democratic Republic of the Congo). Eligible children and adults notified as survivors of Ebola virus disease (ie, who had confirmed Ebola virus disease [RT-PCR positive in blood sample] and were subsequently declared recovered from the virus [RT-PCR negative in blood sample] with a certificate of recovery from Ebola virus disease issued by an Ebola treatment centre) during the 2018-20 Ebola virus disease outbreak were invited to participate in the study. Participants were recruited on discharge from Ebola treatment centres and followed up for 12-18 months depending on recruitment date. Routine follow-up assessments were done at 1, 3, 6, and 12-18 months after inclusion. We collected sociodemographic (age, sex, visit site), clinical (anti-Ebola virus drugs), and laboratory data (RT-PCR and Ct values). The primary outcome was the antibody concentrations against Ebola virus glycoprotein, nucleoprotein, and 40-kDa viral protein antigens over time assessed in all participants. Antibody concentrations were measured by the multiplex immunoassay, and the association between anti-Ebola virus antibody levels and the relevant exposures, such as anti-Ebola virus disease drugs (ansuvimab, REGN-EB3, ZMapp, or remdesivir), was assessed using both linear and logistic mixed regression models. This study is registered at ClinicalTrials.gov, NCT04409405.

Between April 16, 2020, and Oct 18, 2021, 1168 survivors were invited to participate in the Les Vainqueurs d'Ebola cohort study. 787 survivors were included in the study, of whom 358 had data available for antibody responses. 85 (24%) of 358 were seronegative for at least two Ebola virus antigens on discharge from the Ebola treatment centre. The antibody response over time fluctuated but a continuous decrease in an overall linear evolution was observed. Quantitative modelling showed a decrease in nucleoprotein, glycoprotein, and VP-40 antibody concentrations over time (p<0·0001) with the fastest decrease observed for glycoprotein. The probability of being seropositive for at least two antigens after 36 months was 53·6% (95% CI 51·6-55·6) for participants who received ansuvimab, 73·5% (71·5-75·5) for participants who received REGN-EB3, 76·8% (74·8-78·8) for participants who received remdesivir, and 78·5% (76·5-80·5) for participants who received ZMapp.

Almost a quarter of survivors were seronegative on discharge from the Ebola treatment centre and antibody concentrations decreased rapidly over time. These results indicate that monoclonal antibodies might negatively affect the production of anti-Ebola virus antibodies in survivors of Ebola virus disease which could increase the risk of reinfection or reactivation.

The French National Agency for AIDS Research-Emergent Infectious Diseases-The French National Institute of Health and Medical Research, the French National Research Institute for Development, and the European and Developing Countries Clinical Trials Partnership.

For the French translation of the abstract see Supplementary Materials section.

Throughout history, pandemics like the Black Death or the Spanish Flue have periodically wiped out large parts of populations.Today, history repeats itself with the on-going SARSCoV-2 pandemic, which manifests that pandemics still hold the potential to cause devastating impact to global health and economy.To prevent severe illness and death, epidemics have been fought with polyclonal antibodies derived from immunized animals, since this technol. was invented by Behring and Kitasato in 1890 [1].Since then, major advances have occurred in the field of immunotherapy, enabled particularly by the advent of recombinant DNA technol. and a range of discovery methodologies that allow for the generation and manufacture of (human) monoclonal antibodies and antibody fragments [2].These advances strengthen our ability to react to infectious diseases with pandemic potential and have already been put to utility in a number of cases [3].As an example, during the 2014-2016 Ebola outbreak in West Africa, a mixture of three monoclonal antibodies (ZMappTM) originating from two prior antibody mixtures (MB003 and Zmab) were combined and rapidly used for treatment of Ebola infected patients despite lacking prior clin. trials to prove safety and efficacy [4].The antibody mixture was shown to be beneficial to the patients, although it did not reach statistical significance compared to standard of care [5].In addition, therapeutic monoclonal antibodies have been, or are currently being developed for H1N1 [6], SARS, MERS [7], and SARS-CoV-2 [8].While vaccine development is supreme to reduce mortality in a pandemic situation, and convalescent plasma or small mols. sometimes can be used for treatment, an urgent need also exists for fast development of therapeutic monoclonal antibodies as a complement.These antibodies can be administered to groups responding weakly to vaccination, such as immunocompromised patients, or prophylactically as a first line of defense for people at high risk of being infected and/ or becoming severely ill.In addition, if prompt testing to detect infected people is in place, an opportunity may exist to administer antibodies as a precaution and treatment before clin. manifestations occur, thereby possibly reducing the severity of an infection.