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A thread on antibody-dependent enhancement (ADE) in #coronaviruses. While developing vaccines, treating patients with convalescent plasma, and considering immunity passports, we must first understand the complex role of antibodies in #SARS, #MERS and #COVID19. (1/13)
Rabbits infected with MERS develop antibody responses but are not protected upon rechallenge and worsened pulmonary pathology observed. Passive transfer of infected rabbit serum to naïve rabbits not protective and enhances lung inflammation. (2/13) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574614/
Analysis of 9 healthcare workers infected with MERS found most severe cases had highest anti-spike antibody titres. Three asymptomatic patients and one patient with mild disease had no detectable antibody response on the basis of ELISA and IFA. (3/13) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880093/
Macaques vaccinated with MVA encoding full-length SARS-COV spike protein have worsened lung pathology upon rechallenge. Transferring purified anti-spike IgG into naïve macaques results in all recipients developing acute diffuse alveolar damage. (4/13)
https://insight.jci.org/articles/view/123158
https://insight.jci.org/articles/view/123158
SARS-COV ADE is strongly mediated by anti-spike antibodies rather than anti-nucleocapsid antibodies. Diluted sera containing anti-spike IgG can increase in vitro infectivity. (5/13) https://www.sciencedirect.com/science/article/pii/S0006291X14013321
Serum containing anti-spike antibodies enables spike-pseudotyped lentiviral particles to infect human macrophages (which do not express ACE2). Could this similarly allow #SARSCoV2 to enter cell types outside the natural tropism? (6/13)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018502/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018502/
Antibodies targeting the receptor-binding domain (RBD) of the spike protein can cross-neutralize both human and palm civet SARS coronaviruses. Could cross-neutralizing antibodies from previous common cold coronaviruses provide ADE to #SARSCoV2? (7/13) https://www.jimmunol.org/content/176/10/6085.long
Clinical data from SARS shows early seroconversion associated with more severe disease and higher mortality (also correlated with advanced age). 32/347 patients (9.2%) had no detectable antibodies. (8/13) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367364/
A very thorough paper demonstrating immunization with various SARS #coronavirus vaccine constructs results in pulmonary immunopathology after challenge with SARS-COV virus. Consistent findings in multiple animal models. (9/13)
https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0035421&type=printable
https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0035421&type=printable
In #COVID19, anti-spike antibodies higher in elderly/middle-aged patients than young patients. 10/175 (5.7%) of patients have no detectable anti-spike antibodies. Anti-spike antibody titres positively correlate with CRP, an inflammatory biomarker. (10/13) https://www.medrxiv.org/content/10.1101/2020.03.30.20047365v1.full.pdf
Similarly, anti-spike IgG positively correlated with age in #COVID19. Interesting how the relationship between age and antibody titres is more linear in females. Additionally, anti-spike IgG positively correlated with inflammatory marker LDH. (11/13)
https://www.medrxiv.org/content/10.1101/2020.03.20.20039495v1.full.pdf+html
https://www.medrxiv.org/content/10.1101/2020.03.20.20039495v1.full.pdf+html
Questions to consider: Why do some #COVID19 patients not make detectable antibody responses? Do these patients have a more potent CD8+ T-cell (CTL) response? Does cross-reactivity of anti-spike antibodies from previous coronavirus exposure increase risk of severe disease? (12/13)
Are antibodies produced by #SARSCOV2 infection protective from reinfection? If so, how durable is this protection and how long will it last? Do anti-spike antibodies provide ADE and worsen pulmonary immunopathology in #COVID19 comparable to #SARS and #MERS in vivo models? (13/13)
