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mRNA vaccine-induced SARS-CoV-2 spike-specific IFN-γ and IL-2 T-cell responses are predictive of serological neutralization and are transiently enhanced by pre-existing cross-reactive immunity
Figure 1. Comparisons of serological anti-spike IgG antibody levels against HCoV-229E (red), HCoV-HKU1 (blue), HCoV-NL63 (purple), and HCoV-OC43 (grey) between non-cross-reactive and cross-reactive mRNA vaccinees at 2-6 weeks post-second dose. Systemic and Mucosal Antibody Responses to SARS-CoV-2 Variant-Specific Prime-and-Boost and Prime-and-Spike Vaccination: A Comparison of Intramuscular and Intranasal Bivalent Vaccine Administration in a Murine Model
Figure 1. Wu-1, BA.4/5, and NL63 spike-specific IgG titers in serum at the study endpoint for mice intranasally boosted with a 10 μg dose of NL63 seasonal coronavirus protein. Coronaviruses can cause a wide range of respiratory, gastrointestinal and central nervous system diseases in humans and other animals, threatening human health and causing economic losses. However, coronaviruses are able to adapt relatively easily to new environments through mutation and recombination and are therefore able to change host range and tissue tropism efficiently. Understanding coronavirus virology and controlling its spread is important for global health and economic stability.
Coronaviruses are large enveloped positive-stranded RNA viruses in which the genome is encapsulated within a helical capsid formed by a nucleocapsid protein (N) and further surrounded by an envelope. Three structural proteins are associated with the viral envelope, membrane protein (M), envelope protein (E), and spike protein (S). The M and E proteins are involved in viral assembly, and the S protein mediates viral entry into the host cell. The S protein forms huge protrusions on the surface of the virus, giving it the appearance of a crown, hence the name coronavirus. The S protein contains three large segments, a large ectodomain, a single transmembrane anchor, and a short intracellular tail. The ectodomain consists of the receptor binding subunit S1 and the membrane fusion subunit S2. Representative α-coronaviruses include human coronavirus NL63 (HCoV-NL63), porcine transmissible gastroenteritis coronavirus (TGEV), PEDV, and porcine respiratory coronavirus (PRCV). Representative betacoronaviruses include SARS-CoV, MERS-CoV, bat coronavirus HKU4, bovine coronavirus, and human coronavirus OC43.
Figure 1. Cryo–electron microscopy structures of prefusion trimeric coronavirus spikes
(Source: Li F. 2016)
Coronavirus spike proteins mediate the entry of coronaviruses into host cells, where it first binds to a receptor on the host cell surface via the S1 subunit, and then fuses the virus and host membranes via the S2 subunit. Two structural domains in S1 from different coronaviruses recognize various host receptors, leading to viral attachment. In order to fulfill the function of the S protein, it exists in two different conformations structurally, i.e., pre-fusion and post-fusion conformations. During membrane fusion, the virus must trigger a conformational transition of the S protein from pre-fusion to post-fusion. In addition to mediating viral entry, spike proteins are key determinants of viral host range and tissue tropism and major inducers of host immune responses.
HCoV-NL63 S
Human CoV NL63 S
Human coronavirus NL63 S
References
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