Table 1.
Immune responses to EBOV infection in animal models and human survivors.
| Model | Responses to EBOV infection | ||||
|---|---|---|---|---|---|
| Clinical Presentation | Antibody production and protection | CD4+/CD8+ | B cells | NK cells | |
| Human survivors | Range from asymptomatic to flu-like symptoms with continued progression to: vomiting, diarrhoea, rash, kidney and liver damage, haemorrhaging and low white blood cell (84). | Strong and early humoral response is associated with survival (78) (72). | Strong and sustained T cell responses, with reduced expression of inhibitory molecules and a diverse T cell repertoire, are associated with survival (67) (68). Persistent T cell responses are associated with sequalae (71) (72) (73). | Extensive activation during acute infection. Subclass composition changes over time with persistent IgG1, rapid decline of IgG3 and late increase in IgG4 (64). | Increase in survivors and decrease in fatalities (78). |
| Macaques (cynomolgus and rhesus) | Identical to human EVD (85). | Antibodies produced in response to infection contribute to survival (86). | Both CD4+ and CD8+ counts decrease during acute infection stage (45). | Levels in blood remain stable (45). | Decline during acute phase (45) (87). |
| African green monkeys | Identical to human EVD. Rash is less frequent (85). | Protection from natural infection is difficult to determine due to lack of NHP model for mild EVD (88). | Both CD4+ and CD8+ cells show signs of apoptosis and depleted levels in lymph nodes. CD4+ cells increased in germinal centres (44). | Lymphocyte depletion in B cell follicles (44). | ND |
| Mice (mouse-adapted model) | Mouse-adapted virus and intraperitoneal injection required for infection. Unlike humans, EVD does not manifest with rash, coagulopathy or haemorrhagic symptoms. However they can succumb to disease (85). | Protection from antibody transfer has been reported (59) (60) (65). | T cells show drastic depletion during the acute phase (46) but are still important for protection. CD8+ T cells provide protection against acute infection (47) whilst CD4+ T cells confer long-term protection and challenge viral persistence (48). | Important for fighting viral persistence (48). | Drastic depletion in blood during acute phase (46) but accumulation in EBOV infected tissues (89). Differential effects depending on viral load (89). |
| Naïve or immunocompromised mice | Unlike the mouse-adapted model, EVD in this model can manifest with haemorrhagic symptoms (85). | Acquire protection from antibody transfer (90). | Adoptive T cell transfer from vaccinated or infected mice can confer protection against MA-EBOV (91) (47). | ND | NK cells are required for protection against infection, even if they have received prior protection from VLPs (92). |
| Humanised mouse models | Various models capable of recapitulating human EVD (85). Can mimic human EVD, including symptoms of hepatic pathology, lymphocyte apoptosis, haemorrhaging, and lethal outcome when infected with MA-EBOV (88) (93) (94). |
ND | T cell environment varies depending on model. Restricted CD8+ responses reported, with limited MHC interactions (95). CD8+ (and presumed CD4+) T cell activation observed 8 days after inoculation with EBOV (96). |
Can show measurable B cell responses (88) (88) but the B cell compartment is short-lived (95). | Important in early immune response and shows a significant decrease 5 and 8 days after inoculation (96). |
| Ferret | Can be infected with wild-type EBOV and demonstrate human EVD symptoms including rash, coagulation abnormalities and haemorrhaging, not seen with some other models (34) (35). | Acquire protection from antibody transfer (58) (60). | ND | ND | ND |
| Guinea pig | Require Guinea pig-adapted virus. Does not recapitulate rash or haemorrhagic symptoms but EVD does manifest with platelet reduction, liver pathology, and lymphocyte apoptosis (85). | Acquire protection from antibody transfer (55). | ND | ND | ND |
| Hamster Model | Requires adapted EBOV. Recapitulates key features of EVD including coagulopathy and haemorrhaging, absent in many rodent models (97) (98) (85). | Acquire protection from antibody transfer (99). | CD4-dependent antibody responses (99). | ND | ND |
Clinical presentation and adaptive immune responses observed in each species. NA, Not applicable; ND, Not determined.