Ebola Virus: Immune Mechanisms of Protection and Vaccine Development

Abstract

Vaccination is one of our most powerful antiviral strategies. Despite the emergence of deadly viruses such as Ebola virus, vaccination efforts have focused mainly on childhood communicable diseases. Although Ebola virus was once believed to be limited to isolated outbreaks in distant lands, forces of globalization potentiate outbreaks anywhere in the world through incidental transmission. Moreover, since this virus has already been transformed into weapongrade material, the potential exists for it to be used as a biological weapon with catastrophic consequences for any population vulnerable to attack. Ebola hemorrhagic fever (EHF) is a syndrome that can rapidly lead to death within days of symptom onset. The disease directly affects the immune system and vascular bed, with correspondingly high mortality rates. Patients with severe disease produce dangerously high levels of inflammatory cytokines, which destroy normal tissue and microcirculation, leading to profound capillary leakage, renal failure, and disseminated intravascular coagulation. Vaccine development has been fraught with obstacles, primarily of a biosafety nature. Case reports of acutely ill patients with EHF showing improvement with the transfusion of convalescent plasma are at odds with animal studies demonstrating further viral replication with the same treatment. Using mRNA extracted from bone marrow of Ebola survivors, human monoclonal antibodies against Ebola virus surface protein have been experimentally produced and now raise the hope for the development of a safe vaccine.

Incubation Period of Ebola Hemorrhagic Virus Subtype Zaire

“…This method is similar to the procedure proposed by Eichner and Dietz for smallpox incubation periods [25]. The likelihood contribution of each household member who escaped infection, is${\text{e}}^{-\underset{t_0}{\overset{\mathrm{\infty }}{\int }}\lambda \left(\tau \right)d\tau }$and the likelihood contribution of each household member who developed the disease, is$\underset{t_0}{\overset{t_1}{\int }}\lambda \left(t\right)\ast {\text{e}}^{-\underset{t_0}{\overset{t}{\int }}\lambda \left(\tau \right)d\tau }\ast f\left(t_1-t\right)dt,$where t 0 is the time when the index case first developed symptoms and t 1 is the time when the household contact became ill. λ ( t ) is the infection rate at time t (which depends on the type of contact and the stage of the disease in the index case; see Table 1).…”

Ebola from emergence to epidemic: the virus and the disease, global preparedness and perspectives

“…Profound capillary leakage, renal failure, and disseminated intravascular coagulation are observed in persons suffering with severe EVD [31,32]. Unlike normal circumstances wherein antibodies developed against any infectious agent help to get rid of that particular pathogen from body, EBOV utilizes these antibodies along with the complement factor C1 to cause severe cell damage, thereby exaggerating its pathogenesis.…”

“…EBOV glycoprotein (GP) is a crucial target for developing protective humoral immunity. Human monoclonal antibodies developed against the surface protein of EBOV raised hope for a safer vaccine [31]. A combined DNA vaccination and boost with ZEBOV GP-encoding adenoviral vectors resulted in the development of humoral and cellular immune responses in non-human primates such as cynomolgus macaques.…”

Ebola: translational science considerations

“…The complexity in developing a EBOV-specific vaccine is in part the reason why no licensed vaccine is available yet. It is also the case that prior outbreaks, considering their size and relative containment, failed to evoke the response of the national and international scientific community in pursuit of an anti-EBOV vaccine [ 131 , 132 ]. Even in the course of the present epidemic, the call for the development of an effective vaccine protective against Ebola was relatively subdued until EBOV+ patients were identified on European and US soil.…”