Put the following expressions in the proper place of the Discussion.
A. These data suggest
B. In this study, we demonstrate
C. it is critical to emphasize
D. additional research will be required
E. we were unable to determine
Discussion
Individuals who recover from certain viral infections typically develop virus-specific antibody responses that provide robust protective immunity against re-exposure, but some viruses do not generate protective natural immunity, such as HIV-1. Human challenge studies for the common cold coronavirus 229E have suggested that there may be partial natural immunity. However, there is currently no data whether humans who have recovered from SARS-CoV-2 infection are protected from re-exposure. This is a critical issue with profound implications for vaccine development, public health strategies, antibody-based therapeutics, and epidemiologic modeling of herd immunity. _____1_______ that SARS-CoV-2 infection in rhesus macaques provided protective efficacy against SARS-CoV-2 rechallenge.
We developed a rhesus macaque model of SARS-CoV-2 infection that recapitulates many aspects of human SARS-CoV-2 infection, including high levels of viral replication in the upper and lower respiratory tract and clear pathologic evidence of viral pneumonia. Histopathology, immunohistochemistry, RNAscope, and CyCIF imaging demonstrated multifocal clusters of virus infected cells in areas of acute inflammation, with evidence for virus infection of alveolar pneumocytes and ciliated bronchial epithelial cells. ______2_______ the utility of rhesus macaques as a model for SARS-CoV-2 infection for testing vaccines and therapeutics and for studying immunopathogenesis. However, neither nonhuman primate model led to respiratory failure or mortality, and thus further research will be required to develop a nonhuman primate model of severe COVID-19 disease.
SARS-CoV-2 infection in rhesus macaques led to humoral and cellular immune responses and provided protection against rechallenge. Residual low levels of subgenomic mRNA in nasal swabs in a subset of animals and anamnestic immune responses in all animals following SARS-CoV-2 rechallenge suggest that protection was mediated by immunologic control and likely was not sterilizing.
Given the near-complete protection in all animals following SARS-CoV-2 rechallenge, ______3_______ immune correlates of protection in this study. SARS-CoV-2 infection in rhesus monkeys resulted in the induction of neutralizing antibody titers of approximately 100 by both a pseudovirus neutralization assay and a live virus neutralization assay, but the relative importance of neutralizing antibodies, other functional antibodies, cellular immunity, and innate immunity to protective efficacy against SARS-CoV-2 remains to be determined. Moreover, ______4_______ to define the durability of natural immunity.
In summary, SARS-CoV-2 infection in rhesus macaques induced humoral and cellular immune responses and provided protective efficacy against SARS-CoV-2 rechallenge. These data raise the possibility that immunologic approaches to the prevention and treatment of SARS-CoV-2 infection may in fact be possible. However, ______5_______ that there are important differences between SARS-CoV-2 infection in macaques and humans, with many parameters still yet to be defined in both species, and thus our data should be interpreted cautiously. Rigorous clinical studies will be required to determine whether SARS-CoV-2 infection effectively protects against SARS-CoV-2 re-exposure in humans.
A．ABCDE
B．BAEDC
C．ABECD
D．BACDE
