Inspired by this tweet by @TheMenacheryLab, I reached out to the wonderful colleagues at the @serimmune to see if the other mutations found in the B.1.1.7 variant would evade antibody responses generated by the wild type #SARSCOV2. (1/n)
According to this report, B.1.1.7 harbors non-synonymous mutations in the following viral genes, resulting in truncation, deletions and amino acid changes. Would these mutations result in evasion from antibodies generated by wild type virus? (2/n)
To probe this possibility, @serimmune used their technology platform based on bacterial display peptide libraries, next generation sequencing & machine learning to reveal antibody reactivity against WT and B.1.1.7 viral antigens. (3/n)
None of the mutations (orange) are within these dominant epitopes.
(5/n)
Zooming in on the spike mutations, either there was no Ab binding (del69/70, N501Y, T716I, S982A, D1118H) or del144, N501Y, A570D, and P681H resulting in only 2/579 having a reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. (6/n)
A caveat of these analyses is that we are only looking at linear epitopes. Mutations might result in conformational epitope changes that affect Ab binding. However, people make multiple antibodies to the spike protein. (7/n)
As RT above, @TheMenacheryLab has shown functionally that the N501Y mutation in the RBD does not evade existing antibodies’ ability to block replication. (8/n)
So overall, while B.1.1.7 may have enhanced transmission capabilities, it does not appear to evade antibody responses. Antibodies induced by prior infection and vaccines should provide protection. For more read this thread by @hayneswa 👇🏽 (9/n)
It does not mean that viral variants that evade antibodies won’t arise in the future. This is why viral genome surveillance effort is so crucial. (End)
My first tweet of 2021 is going to be about 1 dose vs. 2 dose vaccine. I have tweeted in the past of the immunological advantages of a 2 dose vaccine. However, given the enhanced transmission variants on the rise, we need a modified strategy. (1/n)
We typically give vaccines in more than one dose to increase 1) quantity, 2) quality, 3) longevity of antibody responses. This holds true for most vaccines including mRNA vaccines. Here is what I tweeted about this before. (2/n)
However, the 2 dose vaccine with limited number of vaccine means only half the people getting vaccinated at this time. If the virus is spreading slowly, we want to do the right thing and give the most vulnerable 2 doses and others to wait. (3/n)
What aspects of antibody responses determine the outcome of #COVID19? In this new preprint by @carolilucas@sneakyvirus1 et al., we found that the early timing of antibody response (before 14 days of symptom) in infected person is key to recovery. (1/n)
However, patients with lethal COVID did not have the highest level of anti-S or anti-RBD antibodies. What’s going on? (2/n)
To understand better the features of antibody responses in patients who died vs. survived, we compared their time course. We found a delay in antibody responses in lethal disease. We also noted patients with very high neutralizing Ab (HN) with very early antiviral Abs. (3/n)
How do we look for autoantibodies against a wide range of self antigens? The @aaronmring lab developed a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) against 2,770 extracellular and secreted proteins "exoproteome" 💪🏼 (2/n)
A large fraction of #COVID patients had autoantibodies to multiple self antigens. The more severe the disease, more autoantibodies they had.(3/n)
Here is a thread to explain the findings of this study, that used computational tools to predict T cell reactive sequences in #SARSCOV2 subunit vaccines.
Our adaptive immune system has 2 types of white blood cells known as lymphocytes. T cells and B cells. These lymphocytes give us protection from wide variety of pathogens. Each lymphocyte has unique receptor that detect specific features of a pathogen. (2/n)
B cells detect pathogens structures through antibodies. T cells cannot detect pathogens on their own. They can only “see” pathogen when tiny pieces of viral proteins (peptides) are presented by molecules called major histocompatibility complex (MHC). (3/n)
Do some people have cross-reactive antibodies to #SARSCoV2? If so, who are they? And are these cross-reactive Abs protective against #COVID19? A fascinating study by @KevinWNg et al provides answers. Thread. (1/n)
Do some people have cross-reactive antibodies? The answer is yes. SARS-CoV-2 Spike-reactive IgG was detected in 5 of 34 SARS-CoV-2-uninfected individuals with RT-qPCR-confirmed HCoV infection, as well as in 1 of 31 individuals without recent HCoV infection. (2/n)
Who has cross-reactive anti-spike antibodies? Mostly children and adolescents. The prevalence of SARS-CoV-2 S-reactive IgG antibodies peaked at 62% between 6 and 16 years of age. This age group is also the one in which antibodies to seasonal coronaviruses peak.(3/n)
So happy to see a paper by my graduate student, Daniel Kim, chosen as a spotlight for the @JVirology 👏🏼 Daniel found that HSV-1 genome binds to RUNX1 and represses transcription of viral genes - a possible viral strategy to achieve latent infection. (1/n)
Herpesviruses establish latent infection in neurons and leukocytes that express RUNX1 (transcription factor). Curiously, herpesvirus genomes are enriched in RUNX1 binding sites but not other viruses. (2/n)
Overexpression of RUNX1 but not RUNX3 (a related transcription factor that is not expressed in the cell type in which HSV-1 established latency) blunts HSV-1 infection in vitro. (3/n)