Posts Tagged ‘coronavirus’

Antibody-dependent enhancement in coronaviruses

11 April, 2020

This is a condensation / concatenation of a series of 13 tweets put up recently by someone who tweets as “The Immunologist” with the handle @eclecticbiotech. I was impressed enough by it that I thought it deserved to be all in one piece – and he agreed. He also declined any more accreditation, saying only “No credit necessary. This thread is entirely due to the important work carried out by fellow scientists”.

A thread on antibody-dependent enhancement (ADE) in coronaviruses from The Immunologist.

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.

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.

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.

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.

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.

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?

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?

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.

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

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.

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

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?

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?

Sage questions indeed – and ones that anyone developing vaccines to SARS2 should take seriously.

Answers to questions can be directed to TI on Twitter, or put up here for relaying. Enjoy!

Bats and SARS-CoV: deja vu all over again

1 November, 2013

In 2008, I wrote a blog piece entitled “Who do you bind to, my lovely?”, about a couple of papers on SARS-CoV – the coronavirus that causes severe acute respiratory syndrome.  I closed that piece with the following:

“Adding fuel to the speculative fire is another paper in the same issue: this reports that there is evidence of a recombinant origin for SL-CoVs, and there is probably “…an uncharacterized SLCoV lineage that is phylogenetically closer to S[ARS]CoVs than any of the currently sampled bat SLCoVs.”

So let’s all just wait for the next one, shall we?”

…in connection with the fact that horseshoe bat coronaviruses were VERY similar to SARS-CoV, but bound to different receptors.  And we had to wait five years, but heeeeeere we are… these folk may well have found the missing virus(es) that are directly transmissible from bats to humans:

Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor

 Xing-Yi Ge et al.

Nature (2013) doi:10.1038/nature12711

Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far [! – my comment; the last ones were pretty close…] more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.

So – I told you so…B-)


A novel coronavirus capable of lethal human infections

3 March, 2013

See on Scoop.itIIDMM News

In September 2012, a novel coronavirus was isolated from a patient in Saudi Arabia who had died of an acute respiratory illness and renal failure.The clinical presentation was reminiscent of the outbreak caused by the SARS-coronavirus (SARS-CoV) exactly ten years ago that resulted in over 8000 cases. Sequence analysis of the new virus revealed that it was indeed a member of the same genus as SARS-CoV. By mid-February 2013, 12 laboratory-confirmed cases had been reported with 6 fatalities. The first 9 cases were in individuals resident in the Middle East, while the most recent 3 cases were in family members resident in the UK. The index case in the UK family cluster had travel history to Pakistan and Saudi Arabia. Although the current evidence suggests that this virus is not highly transmissible among humans, there is a real danger that it may spread to other parts of the world. Here, a brief review of the events is provided to summarize the rapidly emerging picture of this new virus.

Coronavirus graphic courtesy of Russell Kightley Media

Ed Rybicki‘s insight:

It is truly amazing how fast things can be done these days: it was only in SEPTEMBER that the new virus was isolated; the latest fatality was literally in the last couple of weeks.  It remains to be seen whether or not it will spread – given its apparent lethality, we can only hope it does not!

See on