Prospects of animal models and their application in studies on adaptive immunity to SARS-CoV-2

Abstract

The adaptive immune response induced by SARS-CoV-2 plays a key role in the antiviral process and can protect the body from the threat of infection for a certain period of time. However, owing to the limitations of clinical studies, the antiviral mechanisms, protective thresholds, and persistence of the immune memory of adaptive immune responses remain unclear. This review summarizes existing research models for SARS-CoV-2 and elaborates on the advantages of animal models in simulating the clinical symptoms of COVID-19 in humans. In addition, we systematically summarize the research progress on the SARS-CoV-2 adaptive immune response and the remaining key issues, as well as the application and prospects of animal models in this field. This paper provides direction for in-depth analysis of the anti-SARS-CoV-2 mechanism of the adaptive immune response and lays the foundation for the development and application of vaccines and drugs.

Keywords: SARS-CoV-2; adaptive immunity; animal model; cross-immune response; immune memory; tissue-resident immune response.

Figure 1

Models of SARS-CoV-2 infection. Three kinds of model can be used to study SARS-CoV-2, including in vitro model cell line, organoid, and in vivo animal models. In contrast with in vitro models, animal models can simulate virus-host interactions observed in human clinical research and have unique advantages in their application.

Figure 2

Clinical features of COVID-19. Based on the receptor (ACE2/TMPRSS2) binding specificity of the Spike protein, SARS-CoV-2 can infect multiple tissues and organs, especially the respiratory tract, lung and intestine. COVID-19 can cause significant lung inflammation, intestinal disturbances, and nerve damage, including loss of smell.

Figure 3

Persistence of adaptive immune responses to SARS-CoV-2. Following infection with SARS-CoV-2, an adaptive immune response is initiated. The viral load peaks at one week, CD4⁺ and CD8⁺ T cells peak at 1-2 weeks, and antibody levels peak at 3-5 weeks. The persistence and protective thresholds of immune memory in cellular and humoral immune responses are currently unknown. The association of preexisting immunity elicited by cross-reactive T-cell immune responses with asymptomatic infection remains to be further investigated.

Figure 4

Antiviral mechanism of the adaptive immune response to SARS-CoV-2. (A) In vivo distribution of virus-specific adaptive immune responses, including circulating and tissue-resident adaptive immune responses. The relationship between circulating immune responses and tissue-resident immune responses remains to be further investigated. The role of lung tissue-resident immune responses in the fight against SARS-CoV-2 infection is worth investigating. (B) Mechanisms of adaptive immune responses against SARS-CoV-2 and their relationship to disease severity.