Ebola Infection May Provide Partial Immunity to Other Filoviruses

Those patients who survive infections caused by the Ebola or Marburg viruses may gain at least partial immunity to other filoviruses through specific antibodies generated during serological immune responses. Furthermore, these antibodies can persist for many years beyond the onset of infection, according to the results of a study published recently in Clinical and Vaccine Immunology.¹

The study was presented by first author Mohan Natesan, PhD, from the Molecular and Translational Sciences Division of the United States Army Medical Research Institute of Infectious Diseases in Frederick, and his colleagues. In describing the rationale for- and timing of the study, Dr. Natesan told Contagion, "There is an urgent need for vaccines and therapeutics that can be used to treat future disease outbreaks and to block virus shedding from chronic Ebola infections. Yet, there are few laboratory methods that provide a comprehensive analysis of antibodies resulting from infection or prospective vaccines. Virus neutralization assays, ELISAs, and similar traditional methods generally address a limited number of pathogens and are costly to perform. The protein microarray method used in our research, is a recent technological development that provides a high-throughput and low cost analysis of biological fluids. Very large panels of recombinant proteins as well as inactivated viruses can be incorporated in small quantities into the microarray to perform many separate assays at the same time."

Dr. Natesan and his colleagues studied protein and virus-specific antibodies from the sera of Marburg marburgvirus (MARG), Bundibugyo (BDBV), and the Filoviridae species Sudan (SUDV) survivors using the aforementioned multiplexed microarray. Of the seven antigens encoded by filovirus genomes, three were focused on in this study. Two conserved antigens, viral protein 40 (VP40) and nucleoprotein (NP), and one highly variable antigen, envelope glycoprotein (GP), were selected because conserved antigens have the potential to capture serological responses against the broadest number of infections, while those that are more variable may be able to detect antibodies that differ between viral variants. VP40, NP, and GP from six species of filoviruses and nine isolates of whole inactivated filoviruses were included in the array. The patient sera examined were collected one, seven, and 14 years after recovery from MARG, BDBV, and SUD, respectively.

The microarray data indicated that antibody responses differed between those infected with MARG, BDBV, and SUD. While sera from those surviving any one of these infections showed significant antibody responses to antigens from the original infecting species, the pattern of additional cross reactivity with other filoviruses varied. For example, NP was found to be the most cross-reactive of the antigens assessed. Conversely, GP was found to be the most specific antigen. Additionally, antibodies from MARG survivors were found to be the least cross-reactive, while the highest cross reactivity was detected amongst survivors of (SUDV). Study results also revealed that antibodies specific for nucleoprotein were detectable up to 14 years after SUDV infection, and that antibodies against VP40, NP, and GP remained significantly elevated 7 years after the outbreak of (BDBV) infections.

"Our study suggests that survival from infection caused by one species may impart at least partial immunity to other filoviruses, and specific antibodies are maintained for years after infection. Concurrent detection of antibody responses to multiple antigens from one species using the microarray system may increase accuracy of results, while the inclusion of probes for multiple viral species facilitates a broader, high-throughput, analysis of infection history," Dr. Natesan said.

Regarding the broader implications of his team's study results, Dr. Natesan told Contagion, "The severe shortage of diagnostic assays and medical interventions during the recent Ebola epidemic motivated us to develop a better way to examine immune responses to infection. We envision that the microarray assay may be particularly useful for disease surveillance among human and potential zoonotic populations."

William Perlman, PhD, CMPP is a former research scientist currently working as a medical/scientific content development specialist. He earned his BA in Psychology from Johns Hopkins University, his PhD in Neuroscience at UCLA, and completed three years of postdoctoral fellowship in the Neuropathology Section of the Clinical Brain Disorders Branch of the National Institute of Mental Health.

References

1. Natesan M, Jensen SM, Keasey SL, et al. Human survivors of disease outbreaks caused by Ebola or Marburg viruses exhibit cross-reactive and long-lived antibody responses. Clin Vaccine Immunol. 2016 Jun 22. pii: CVI.00107-16. [Epub ahead of print].