Vipin M. Vashishtha Profile picture
Pediatrician, ‘rational’ vaccine thinker, Editor Covid-19 Vaccines, Textbook on Vaccines & many other books on vaccines, Past-Convener IAP COI, Member-WHO-VSN
Hardik Desai Profile picture Misha🐭 Profile picture @The_Colbobs@m/st/Ⓥ ⚛️ 🗿 Profile picture 4 subscribed
Mar 22 5 tweets 2 min read
An exosome based protein subunit SARS2 vaccine induced a potent humoral immune response as demonstrated by high levels of NAbs not only against the Delta SARS2 virus but also two Omicron variants (BA.1 and BA.5), providing broader protection than current mRNA vaccines. 1/ Additionally, both CD4+ and CD8+ T cell responses were increased significantly after treatment.
Quantification of spike protein by ELISA showed that only nanograms of protein were needed to induce a potent immune response. 2/
Mar 11 8 tweets 2 min read
A new study describes 4 future scenarios of Covid19 based on accumulation of immunity w/ subsequent infections or vaccinations

🟠 Scenario I: the most optimistic case; rapid accumulation of immunity, combined w/ a strong reduction in susceptibility following 1st exposure 1/ ➡️ This combination leads to strong population immunity (i.e., low average susceptibility) and thus very few cases once the third peak has abated. While this Scenario is very unlikely to be attained at this stage unless more robust vaccines (or possibly antivirals) emerge 2/
Mar 10 17 tweets 6 min read
What’s common between Inactivated Polio Vaccine, Acellular pertussis vaccine and most Covid19 vaccines? They provide reasonably good to excellent individual protection against polio, whooping cough & Covid, respectively.
But one more thing that ‘club’ them together… 1/ They fail to provide adequate protection against the infection and transmission of these three diseases. Why?
They lack robust mucosal immunity at the portal of entry of the organisms responsible for these diseases. 2/
Mar 10 10 tweets 2 min read
Strong immune responses are needed to control SARS2 infection & disease. NAbs activity has dominated as a surrogate measure of protection.
However, protection ag severe disease w/out robust neutralisation suggests that other limbs of immunity—T cells & NK cells, play a role 1/ Vaccination produced antibodies (Abs) that only weakly induced antibody-dependent cellular cytotoxicity (ADCC), however, Abs from individuals who were infected prior to vaccination (hybrid immunity) elicited much stronger anti-spike ADCC. 2/ Image
Mar 10 5 tweets 2 min read
Does temperature at human nasal epithelium affect viral replication of Influenza-A (IAV) & SARS2?

In a new study, researchers investigated the effect of temperature on host responses in human nasal epithelial cells (hNECs) utilizing IAV and SARS2 in vitro infection models. 1/ They demonstrate that temperature affects SARS2, but not IAV, viral replicative fitness and that SARS2 infected cultures are slower to mount an infection-induced response, likely due to suppression by the virus. 2/
Feb 4 7 tweets 2 min read
Omicron's basic reproduction number (R0) has been close to 20 or higher. However, it is not known what caused such an extremely high R0.

A new study aims to find an explanation for such high R0 Omicron infection 👇 1/ Researchers found that the gene PTAFR (Platelet Activating Factor Receptor) is highly correlated with Omicron variants, and so is the gene CCNI (Cyclin I), which is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog. 2/
Feb 3 4 tweets 2 min read
A new RCT of a second boost with either the BNT162b2 (30 mcg) WT/BA.1 or WT/ BA.4/5 updated boosters against homologous and heterologous strains including BQ.1.1 and XBB.1. 1/ Early immunogenicity results demonstrate better neutralization against BA.4/5 with the WT/BA.4/5 vaccine booster. 2/
Feb 3 4 tweets 1 min read
In a cohort of 280 adults with prior SARS2 infection, researchers assessed the presence & types of LongCovid (LC) symptoms and prior medical history (including COVID-19 history and HIV status) and performed serological testing for Epstein Barr Virus (EBV) and CMV 1/ They observed that LC symptoms, such as fatigue & neurocognitive dysfunction, at a median of 4 mo following initial diagnosis were independently associated w/ serological evidence suggesting recent EBV reactivation, but not with ongoing EBV viremia. 2/
Feb 2 5 tweets 2 min read
Several studies have confirmed the presence of SARS2 reactive CD4+ & CD8+ T cells in hospitalized patients. However, it is unclear if specific T-cell subsets are responsible for differences in disease severity. 1/ A new research now shows that patients with severe COVID19 had greater frequencies of CD4+ T cells expressing CD62L compared to non-severe patients and greater frequencies of perforin+ CD8+ T cells compared to recovered patients. 2/
Jan 18 8 tweets 2 min read
Recent reports have shown that the relationship between immunosenescence and COVID 19 can be bidirectional, since hospitalized patients with severe COVID have an accumulation of senescent T cells suggesting that immunosenescence can be also exacerbated by SARS2 infection 1/ This study performed on two different populations from Portugal and Brazil, identified their distinctive inflammatory profile and provided evidence of increased frequencies of senescent and exhausted T cells within a seven day period in patients with mild to severe COVID 19 2/
Jan 17 4 tweets 2 min read
Great news!
Gene therapy from bench to bedside! Microdystrophin for dystrophic dogs: one step closer to clinical use in DMD patients! 1/ Researchers conducted a blinded, placebo-controlled 90-day study of systemic administration of an adeno-associated virus (AAV) vector carrying a canine microdystrophin-5 transgene in golden retrievers dogs with muscular dystrophy 2/ Image
Jan 17 15 tweets 3 min read
The protective efficacy of serum antibodies results from the interplay of antigen-specific B cell clones of different affinities and specificities. These cellular dynamics underlie serum-level phenomena such as “Original Antigenic Sin” (OAS) 1/ OAS means a proposed propensity of the immune system to rely repeatedly on the first cohort of B cells engaged by an antigenic stimulus when encountering related antigens, to the detriment of inducing de novo responses
Jan 16 6 tweets 2 min read
A link between immunosuppression & COVID-19?

A previously healthy female came +ve for COVID & was later diagnosed w/ cryptococcal meningitis.
While her diagnosis in itself was unusual, her disease progression was even more baffling, as would be found in an immunocompromised This disease progression raises questions as to what role SARS2 virus plays in the innate, adaptive, and overall host factors leading to immunosuppression.…
Jan 16 6 tweets 2 min read
Gone are the days of a single variant dominating and sweeping the entire globe. Now we are having a swarm of sub-variants with a country level, regional dominance. This may be the reason why the WHO is still holding back assignment of a new Greek letter to some of them So, the days of high amplitude, frequent waves have also gone. Thanks to a gradually building population immunity.
“Now the waves will be more spaced, only becoming possible when in a sufficient no. of people the NAb levels have waned to allow infection” @Marc_Veld
Jan 9 5 tweets 1 min read
From the start of the pandemic, a prominent pattern of demyelination of nervous system has emerged, suggesting an underlying mechanism of viral mimicry to CNS proteins. 1/ It is hypothesized that immunodominant epitopes of SARS2 share homology with proteins associated with multiple sclerosis (MS). 2/
Jan 8 6 tweets 2 min read
SARS2 VOCs possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8+ T cell-mediated immunity by VOC. 1/ Here, researchers demonstrated that all SARS2 VOCs possess the ability to suppress MHC I expression. They identified several viral genes that contribute to the suppression of MHC I expression. 2/
Jan 8 12 tweets 3 min read
There is emerging evidence that nucleocapsid (N) protein specific antibody responses may be protective.

The N protein is one of the most abundant, highly conserved RNA-binding proteins, which plays an important role in the packing of the SARS2 genome. 1/ A high frequency of polyfunctional T cell responses specific for certain epitopes within the N protein was found to associate with milder illness 2/
Jan 7 5 tweets 2 min read
The existence of multiple disulfide bonds in Spike protein makes it potentially susceptible to reductive cleavage.
Researchers evaluated impact of chemical reduction on Spike proteins from different variants & found that those from Omicron are highly vulnerable to reduction 1/ Image Furthermore, they found that alterations in the RBM are the major determinants of this vulnerability.

Specifically they discovered that Omicron mutations facilitate cleavage of C480-C488 & C379-C432 disulfides, which consequently impairs binding activity & protein stability. 2/ Image
Jan 6 6 tweets 2 min read
The activity of monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. 1/ Researchers followed a cohort of COVID patients hospitalized during the early waves of the pandemic for 6-7 months. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS2 infection. 2/ Image
Jan 6 6 tweets 2 min read
Can Spike protein+obesity exacerbate LongCovid (PACS)-related cardiomyopathy?

To study this association, researchers developed Spike protein-pseudovirus with the proper surface tropism of SARS2 for viral entry assay in vitro & administration into high fat diet (HFD)-fed mice. 1/ ImageImage They found LDL cholesterol enhanced viral uptake in endothelial cells, macrophages & cardiomyocytes.

Selective cardiac and adipose viral depositions were observed in HFD mice but not in normal-chow-fed mice. 2/
Jan 6 10 tweets 3 min read
Acute viral infections can have durable impacts on the immune system long after recovery, but how they affect immune states and responses to future vaccination against a different antigen remain poorly understood 1/ A new study shares interesting findings of sex-specific differences in immune responses following mild Covid infection and how this infection shapes immune responses to subsequent influenza vaccination. 2/…