Table 1.
Immunological Features of SARS-CoV-2 Infection in Animal Models of COVID-19
| Animal Model | Innate Immunity | Adaptive Immunity | Vaccine Design/Therapeutic mAbs |
|---|---|---|---|
| Rhesus macaque | Observed initial cytokine surge within wk 1; infiltration of myeloid cells into lungs; mild neutropenia21,44,45 | Exposure results in protective B and T-cell responses by 21 DPI, protective against reinfection. The higher the inoculum, the stronger the adaptive immune response. T cell infiltrates into lungs; mild lymphopenia118 | DNA vaccine induced strong B- and T-cell responses that were protective against a high inoculum challenge, nAbs were on the order of what is observed in convalescent human serum162; Adeno (ChAd)-vectored vaccine elicited a robust humoral and T-cell–mediated response and provided protection from subsequent challenge45; purified inactivated virus vaccine provided protection from challenge160 |
| Cynomologus macaque | No studies to date | Seroconversion by 14 DPI117, no studies to date on T-cell responses | Recombinant protein vaccine induced high nAbs titers, no challenge work to date158 |
| Pigtailed macaque | No studies to date | No studies to date | RNA vaccine induced high nAbs titers, no challenge work to date159 |
| African green monkeys (AGM) | Observed initial cytokine surge within wk 1, mild thrombocytopenia, myeloid cell infiltration in lungs19,22,46,47 | Seroconverted by 5 DPI peaked 15 DPI with high titers of nAbs,19,22 no T-cell studies to date | No studies to date |
| Ferret | Observed innate cells infiltration in lung, associated with pathology; no virus detected in brain43 | Seroconversion of all animals by terminal time point, had varying titers of nAbs based on dose and inoculation route; no T-cell studies to date; protected from rechallenge109 | No studies to date |
| Syrian hamster | Observed initial cytokine surge within wk 1,18 attributed lung pathology to type I IFN responses, mononuclear cell infiltration in lungs of infected animals.24 No virus detected in brain68 | Seroconversion of all animals, nAb detected by 14 DPI18,107; no T-cell studies to date; no rechallenge studies to date | No vaccine studies to date; mAb and convalescent serum prophylactic studies showed protection107,111 |
| Cat | No studies to date | Seroconversion of all animals, nAb detected by 20 DPI43; Abs/nAbs are found in domestic and stray cats without known exposure110: no T-cell studies to date | No studies to date |
| Dog | No studies to date | <50% of animals inoculated seroconverted, no exposed animals seroconverted43; no T-cell studies to date | No studies to date |
| Pig | No studies to date | No animals seroconverted43; no T-cell studies to date | No studies to date |
| Mouse adapted SARS-CoV-2 | Observed initial cytokine surge in aged mice; inflammatory cell infiltration into lungs of young and old mice; Type III IFN may play a protective and therapeutic role25 | Not assessed except in context of vaccination | Recombinant protein or virus replicon particle vaccination lead to protection on challenge25,161; strong nAbs developed in response to vaccine; A mAb prophylactic study showed protection112; T cells not assessed |
| Knockin –CRISPR/Cas9—hACE2 mouse | Observed initial cytokine surge in aged mice; inflammatory cell infiltration into lungs of young and old mice, neutrophils and macrophages; SARS-CoV-2+ macrophages in lung42; viral RNA detected in brain | No studies to date | No studies to date |
| hACE2 transgenic mouse (driven by mouse promoter) | Inflammatory cell infiltration into alveolar interstitium and alveolar spaces39 | All inoculated animals seroconverted, 50% of exposed cage mates seroconverted108; no T-cell studies to date | No vaccine studies to date; A mAb prophylactic study showed protection.112 |
| HFH4-hACE2 transgenic mouse | Observed monocyte and lymphocyte infiltration into lung; viral RNA detected in brain; cytokines not assessed41 | Animals that survived long term seroconverted and were protected from reinfection41 | No studies to date |
| K18-hACE2 transgenic mouse | Observe initial cytokine surge in blood and tissues 2–4 DPI20; early recruitment of alveolar macrophages, monocytes, and neutrophils in BAL, viral RNA detected in brain,64,65,163 possibly due to aggressiveness of model56,64,66,67 | No studies to date | No studies to date |
| Adeno-associated virus 9 (AdV9)—hACE2 induced mouse | Increase in activated monocytes, macrophages, neutrophils, and NK cells in lung; have similar IFN signatures to COVID patients; Type I IFN drive pathogenic response27 | Seroconversion of all animals, nAbs detected by 7 DPI; increase in activated T cells in lung27 | No studies to date |
| Adenoviral (Ad5)—hACE2 induced + IFNAR blockade mouse | Observed immune cell infiltrates into lung; increase in proinflammatory cytokines in lung; Type 1 IFN signaling shown to be protective early in infection26 | No studies to date | No vaccine studies to date; A mAb prophylactic study showed protection26 |
wk= week; DPI= days post infection; IFN= interferon; nAb= neutralizing antibodies; mAb= monoclonal antibodies, NK= natural killer; BAL= Bronchoalveolar lavage.