UK begins rollout of Moderna COVID vaccine

 Britain begins rolling out Moderna’s COVID-19 vaccine on Wednesday in Wales and expects to be using it in the rest of the United Kingdom in the coming days in a boost to the country’s health system after supplies of shots started to slow.

Moderna will become the third vaccine to be used in Britain after the Oxford-AstraZeneca and Pfizer jabs and comes as the supply of shots from Astra starts to slow due to manufacturing issues including at a site in India.

“I’m delighted we can start the UK rollout of the Moderna vaccine in west Wales today,” Hancock said. “Today we start with the third approved vaccine. Wherever you live, when you get the call, get the jab.”

Prime Minister Boris Johnson urged people to get their shots as soon as they were invited.

The United Kingdom has vaccinated 31.6 million people with a first dose of a COVID-19 vaccine - and administered 5.5 million second doses. It will soon have vaccinated half of its total population.

Junior business minister Paul Scully told Sky News the Moderna shot, which uses the same mRNA technology as Pfizer but is easier to transport, will be coming to the rest of the United Kingdom in the coming days.

“You’ve heard the vaccine minister Nadhim Zahawi talking about the third week of April. We’re already just about to start the second week of April so that’s not too long to wait.”

Israel is the world leader in vaccinating its population against COVID, followed by the United Arab Emirates, Chile, the United Kingdom, the United States, Bahrain, Serbia and Hungary, according to Our World in Data.

https://www.reuters.com/article/us-health-coronavirus-britain-moderna/uk-begins-rollout-of-moderna-covid-vaccine-idUSKBN2BU0KG

Natural mucosal barriers and COVID-19 in children

 

Carl A. Pierce,1 Sharlene Sy,2 Benjamin Galen,3 Doctor Y. Goldstein,4 Erika P. Orner,4 Marla J. Keller,3 Kevan C. Herold,5 and Betsy C. Herold2

DOI: https://doi.org/10.1172/jci.insight.148694

PDF: https://insight.jci.org/articles/view/148694/pdf

Abstract

Background: COVID-19 is more benign in children compared to adults for unknown reasons. This contrasts with other respiratory viruses where disease manifestations are often more severe in children. We hypothesize that a more robust early innate immune response to SARS-CoV-2 protects against severe disease.

Methods: Clinical outcomes, SARS-CoV-2 viral copies and cellular gene expression were compared in nasopharyngeal swabs obtained at the time of presentation to the Emergency Department from 12 children and 27 adults using bulk RNA sequencing and quantitative reverse transcription PCR. Total protein, cytokines and anti-SARS-CoV-2 IgG and IgA were quantified in nasal fluid.

Results: SARS-CoV-2 copies, ACE2 and TMPRSS2 gene expression were similar in children and adults, but children displayed higher expression of genes associated with interferon signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-α2, IFN-γ, IP-10, IL-8, and IL-1β protein were detected in nasal fluid in children versus adults. Children also expressed higher levels of genes associated with immune cells whereas expression of those associated with epithelial cells did not differ in children versus adults. Anti-SARS-CoV-2 IgA and IgG were detected at similar levels in nasal fluid from both groups. None of the children required supplemental oxygen whereas 7 adults did (p=0.03); four adults died.

Conclusions: These findings provide direct evidence of a more vigorous early mucosal immune response in children compared to adults and suggest that this contributes to favorable clinical outcomes.

https://insight.jci.org/articles/view/148694

Detection of SARS-CoV-2 antibodies in response to BNT162b2, mRNA-1237 mRNA vaccine by commercial antibody tests

  

View ORCID ProfileJamil N Kanji, Ashley Bailey, Jayne Fenton, Sean H. Ling, Rafael Rivera, Sabrina Plitt, Wendy I Sligl, Sean C Taylor, LeeANn Turnbull, Graham Tipples, Carmen L Charlton

doi: https://doi.org/10.1101/2021.03.30.21254604

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.03.30.21254604v1.full.pdf

Abstract

PURPOSE With rapid approval of SARS-CoV-2 vaccines, the ability of clinical laboratories to detect vaccine-induced antibodies with available high-throughput commercial assays is unknown. We aimed to determine if commercial serology assays can detect vaccine-induced antibodies (VIAs) and understand the vaccination response. METHODS This cohort study recruited healthcare workers and residents of long-term care facilities (receiving the BNT162b2 and mRNA-1273 products, respectively) who underwent serum collection pre-vaccination (BNT162b2 group), 2-weeks post vaccination (both groups), and pre-2nd dose (both groups). Sera were tested for the presence of SARS-CoV-2 IgG using four commercial assays (Abbott Architect SARS-CoV-2 IgG, Abbott Architect SARS-CoV-2 IgG II Quant, DiaSorin Liaison Trimeric S IgG, and GenScript cPASS) to detect VIAs. Secondary outcomes included description of post-vaccination antibody response and correlation with neutralising titers. RESULTS 225 participants (177 receiving BNT162b2 and 48 receiving mRNA-1273) were included (median age 41 years,; 66-78% female). Nucleocapsid IgG was found in 4.1% and 21.9% of the BNT162b2 (baseline) and mRNA-1273 (2-weeks post first dose). All anti-spike assays detected antibodies post-vaccination, with an average increase of 87.2% (range 73.8-94.3%; BNT162b2), and 25.2% (range 23.8-26.7%; mRNA-1273) between the first and last sampling time points (all p<0.05). Neutralising antibodies were detected at all post-vaccine timepoints for both vaccine arms, with increasing titers over time (all p<0.05). CONCLUSION Anti-spike vaccine-induced SARS-CoV-2 IgG are detectable by commercially available high-throughput assays and increases over time. Prior to second dose of vaccination, neutralising antibodies are detectable in 73-89% of individuals, suggesting the majority of individuals would have some degree of protection from subsequent infection.

Competing Interest Statement

Dr. Sean Taylor is an employee of GenScript USA. He assisted in providing interpretation of the GenScript assay used in this study. He had no role in the design of the study or the formal data analysis, but did provide suggestions for the final draft which were incorporated after review by the other authors. None of the other authors had conflicts to declare with respect to this manuscript.

Funding Statement

This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors, however testing kits were provided in-kind by all manufactures.

https://www.medrxiv.org/content/10.1101/2021.03.30.21254604v1

Majority of uninfected adults show pre-existing antibody reactivity against SARS-CoV-2

 

Abdelilah Majdoubi,1 Christina Michalski,2 Sarah E. O’Connell,3 Sarah Dada,1 Sandeep R. Narpala,3 Jean P. Gelinas,4 Disha Mehta,4 Claire Cheung,1 Dirk F.H. Winkler,5 Manjula Basappa,3 Aaron C. Liu,1 Matthias Görges,6 Vilte E. Barakauskas,7 Michael A. Irvine,8 Jennifer Mehalko,9 Dominic Esposito,9 Inna Sekirov,10 Agatha N. Jassem,10 David M. Goldfarb,1 Steven Pelech,5 Daniel C. Douek,3 Adrian B. McDermott,3 and Pascal M Lavoie2

DOI:  https://doi.org/10.1172/jci.insight.146316

PDF: https://insight.jci.org/articles/view/146316/pdf

Abstract

Pre-existing cross-reactivity to SARS-CoV-2 may occur in absence of prior viral exposure. However, this has been difficult to quantify at the population level due to a lack of reliably defined seroreactivity thresholds. Using an orthogonal antibody testing approach, we estimated that ~0.6% of non-triaged adults from the greater Vancouver area, Canada between May 17th and June 19th 2020 showed clear evidence of a prior SARS-CoV-2 infection, after adjusting for false-positive and false-negative test results. Using a highly sensitive multiplex assay and positive/negative thresholds established in infants in whom maternal antibodies have waned, we determine that more than 90% of uninfected adults showed antibody reactivity against the spike, receptor-binding domain (RBD), N-terminal domains (NTD) or the nucleocapsid (N) protein from SARS-CoV-2. This sero-reactivity was evenly distributed across age and sex, correlated with circulating coronaviruses reactivity, and was partially outcompeted by soluble circulating coronaviruses’ spike. Using a custom SARS-CoV-2 peptide mapping array, we found that this antibody reactivity broadly mapped to spike, and to conserved non-structural viral proteins. We conclude that most adults display pre-existing antibody cross-reactivity against SARS-CoV-2, which further supports investigation of how this may impact the clinical severity of COVID-19 or SARS-CoV-2 vaccine responses.

https://insight.jci.org/articles/view/146316

Rare disease biotech Reneo Pharmaceuticals sets terms for $100M IPO

 Reneo Pharmaceuticals, a Phase 2 biotech developing therapies for rare genetic mitochondrial diseases, announced terms for its IPO on Monday.

The San Diego, CA-based company plans to raise $100 million by offering 6.3 million shares at a price range of $15 to $17. At the midpoint of the proposed range, Reneo Pharmaceuticals would command a fully diluted market value of $425 million.

The company's sole candidate, REN001, is being developed to modulate genes critical to metabolism and generation of ATP, which is the primary source of energy for cellular processes. REN001 is currently in a Phase 2b trial for primary mitochondrial myopathies, with data expected in 2023, and two Phase 1b trials for long-chain fatty acid oxidation disorders and glycogen storage disease type V, with data expected for both in the 1H22.

Reneo Pharmaceuticals was founded in 2014 and plans to list on the Nasdaq under the symbol RPHM. Jefferies, SVB Leerink and Piper Sandler are the joint bookrunners on the deal.

Relevant Profile: RPHM

https://www.renaissancecapital.com/IPO-Center/News/80361/Rare-disease-biotech-Reneo-Pharmaceuticals-sets-terms-for-$100-million-IPO

Swiss rare disease biotech VectivBio Holding sets terms for $128M US IPO

 VectivBio Holding, a Swiss Phase 3 biotech developing therapies for rare gastrointestinal disorders, announced terms for its IPO on Monday.

The Basel, Switzerland-based company plans to raise $128 million by offering 7.5 million shares at a price range of $16 to $18. At the midpoint of the proposed range, VectivBio Holding would command a fully diluted market value of $634 million.

The company's current product pipeline is focused on rare gastrointestinal disorders. Its candidate, apraglutide, is a next generation, long-acting synthetic peptide analog of glucagon-like peptide-2 (GLP-2) being developed for a range of rare GI diseases, with an initial focus on short bowel syndrome (SBS). Apraglutide is currently being evaluated in a global Phase 3 trial for the treatment of SBS-IF, with topline results expected in the 2H23.

VectivBio Holding was founded in 2019 and plans to list on the Nasdaq under the symbol VECT. BofA Securities, SVB Leerink, and Credit Suisse are the joint bookrunners on the deal. It is expected to price during the week of April 5, 2021.

Relevant Profile: VECT

https://www.renaissancecapital.com/IPO-Center/News/80369/Swiss-rare-disease-biotech-VectivBio-Holding-sets-terms-for-$128-million-US

SPAC Innovatus Life Sciences Acquisition files for a $175M IPO

  Innovatus Life Sciences Acquisition, a blank check company formed by Innovatus Capital targeting the life sciences sector, filed on Tuesday with the SEC to raise up to $175 million in an initial public offering.

The New York, NY-based company plans to raise $175 million by offering 17.5 million shares at $10. No warrants will be included in the offering. Millennium Management, the Teacher Retirement System of Texas, Corbin Capital, and Innovatus Capital have indicated interest in purchasing an aggregate 39% of the offering. At the proposed deal size, Innovatus Life Sciences Acquisition will command a market value of $225 million.

The company is led by CEO and Chairman David Schiff, who has served as a Partner at Innovatus Capital Partners since 2015 and previously was a Partner at Perella Weinberg Partners. He is joined by CFO and Director Andrew Hobson, who has served as a Partner and CFO of Innovatus Capital Partners since 2016 and was CFO of Univision Communications prior to that. Innovatus Life Sciences Acquisition intends to focus on industries that complement its management team’s background and ability to identify promising opportunities in the life sciences sector.

Innovatus Life Sciences Acquisition was founded in 2021 and plans to list on the Nasdaq under the symbol ILAC. It filed confidentially on March 5, 2021. UBS Investment Bank is the sole bookrunner on the deal.

Relevant Profile: ILAC

https://www.renaissancecapital.com/IPO-Center/News/80440/SPAC-Innovatus-Life-Sciences-Acquisition-files-for-a-$175-million-IPO