18 March COVID Immunity and vaccine

Dear colleagues,

In attachment, you will find some recent papers about immunity and COVID-19. I have highlighted some keywords and phrases in yellow. Some things I noticed are:

1. The intrinsically higher pathogenicity of SARS, MERS and COVID may be due to the structure of the S1 trimer, which "samples" in these viruses (as opposed to the more harmless Coronaviruses) between a closed and an open configuration.
2. COVID 19 has a furin cleavage site between the receptor-binding S1 and the fusion protein (S2), which, however, can be mutated away apparently without loss of infectiousness (in vitro).
3. SARS and COVID-19 also use a widely distributed receptor ACE-2, with type-2 alveolar cells in the lung being the target cell. These are the producers of surfactant, which is important in controlling the surface tension at the air-liquid interface.
4. These pathogenic viruses interfere with the type 1 IFN response (which is delayed first and then hyperactive) and, on the other hand, causes hyper-inflammation (cytokine storm).
5. SARS, MERS and COVID do induce antibody responses that are neutralizing in vitro. For SARS and MERS, slow emergence and low antibody titers were associated with poor prognosis. BUT the possibility of antibody-mediated enhancement (ADE) has also been suggested by several lines of evidence (including feline infectious peritonitis virus or FIPV). It is therefore not excluded that antibodies against other (harmless) human Coronaviruses play a pathogenic role in COVID-19 infection. In addition, this phenomenon could complicate vaccine development (as with Dengue).
6. T cell immunity is important, but not yet well studied in COVID. In SARS, there is hard to interpret data. On the one hand association with Th2 and Neutralizing Ab, on the other hand paradoxical association between polyfunctional CD8 T cells and serious disease.
7. There is strong conservation of especially T cell epitopes between SARS and COVID, which can bind cumulatively with most human MHC class I alleles. Theoretically, therefore, a cross-reacting T cell vaccine can be made.
8. B cell epitopes do not include the receptor-binding site. Otherwise, mouse antisera that neutralize in vitro are more likely to target S2 (the fusion protein).
9. Moderna already has a candidate vaccine based on the mRNA of “a protein found on the coronavirus outer shell” in phase 1 in humans today.

Best, 

Guido Vanham