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SARS-CoV-2 proteins

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    Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals

    Authors: Talia Kustin; Noam Harel; Uriah Finkel; Shay Perchik; Sheri Harari; Maayan Tahor; Itamar Caspi; Rachel Levy; Michael Leschinsky; Shifra Ken Dror; Galit Bergerzon; Hala Gadban; Faten Gadban; Eti Eliassian; Orit Shimron; Loulou Saleh; Haim Ben-Zvi; Doron Amichay; Anat Ben-Dor; Dana Sagas; Merav Strauss; Yonat Shemer Avni; Amit Huppert; Eldad Kepten; Ran D Balicer; Doron Nezer; Shay Ben-Shachar; Adi Stern

    doi:10.1101/2021.04.06.21254882 Date: 2021-04-09 Source: medRxiv

    The SARS-CoV-2 pandemic has been raging for over a year, creating global detrimental impact. The BNT162b2 mRNA vaccine has demonstrated high protection levels, yet apprehension exists that several variants of concerns (VOCs) can surmount the immune defenses generated by the vaccines. Neutralization assays have revealed some reduction in neutralization of VOCs B.1.1.7 and B.1.351, but the relevance of these assays in real life remains unclear. Here, we performed a case-control study that examined whether BNT162b2 vaccinees with documented SARS-CoV-2 infection MESHD were more likely to become infected with B.1.1.7 or B.1.351 compared with unvaccinated individuals. Vaccinees infected at least a week after the second dose were disproportionally infected with B.1.351 (odds ratio of 8:1). Those infected between two weeks after the first dose and one week after the second dose, were disproportionally infected by B.1.1.7 (odds ratio of 26:10), suggesting reduced vaccine effectiveness against both VOCs under different dosage/timing conditions. Nevertheless, the B.1.351 incidence in Israel to-date remains low and vaccine effectiveness remains high against B.1.1.7, among those fully vaccinated. These results overall suggest that vaccine breakthrough infection MESHD is more frequent with both VOCs, yet a combination of mass-vaccination with two doses coupled with non-pharmaceutical interventions control and contain their spread.

    Chimeric spike mRNA vaccines protect against sarbecovirus challenge in mice

    Authors: David R. Martinez; Alexandra Schaefer; Sarah R. Leist; Gabriela De la Cruz; Ande West; Elena N. Atochina-Vasserman; Robert Parks; Maggie Barr; Dapeng Li; Boyd Yount; Drew Weissman; Barton Haynes; Stephanie A. Montgomery; Ralph S. Baric

    doi:10.1101/2021.03.11.434872 Date: 2021-03-12 Source: bioRxiv

    The emergence of SARS-CoV and SARS-CoV-2 MESHD in the 21st century highlights the need to develop universal vaccination strategies against the SARS-related Sarbecovirus subgenus. Using structure-guided chimeric spike designs and multiplexed immunizations, we demonstrate protection against SARS-CoV, SARS-CoV-2 MESHD, and bat CoV (BtCoV) RsSHC014 challenge in highly vulnerable aged mice. Chimeric spike mRNAs containing N-terminal domain (NTD), and receptor binding domains (RBD) induced high levels of broadly protective neutralizing antibodies against three high-risk sarbecoviruses: SARS-CoV MESHD, RsSHC014, and WIV-1. In contrast, SARS-CoV-2 mRNA vaccination not only showed a 10 to >500-fold reduction in neutralizing titers against heterologous sarbecovirus strains, but SARS-CoV MESHD challenge in mice resulted in breakthrough infection MESHD including measurable lung pathology. Importantly, chimeric spike mRNA vaccines efficiently neutralized both the D614G and the South African B.1.351 variants of concern despite some reduction in neutralization activity. Thus, multiplexed-chimeric spikes may provide a novel strategy to prevent pandemic and SARS-like zoonotic coronavirus infections MESHD, while revealing the limited efficacy of SARS-CoV-2 spike PROTEIN vaccines against other sarbecoviruses.

    Decreased SARS-CoV-2 MESHD viral load following vaccination

    Authors: Matan Levine-Tiefenbrun; Idan Yelin; Rachel Katz; Esma Herzel; Ziv Golan; Licita Schreiber; Tamar Wolf; Varda Nadler; Amir Ben-Tov; Jacob Kuint; Sivan Gazit; Tal Patalon; Gabriel Chodick; Roy Kishony

    doi:10.1101/2021.02.06.21251283 Date: 2021-02-08 Source: medRxiv

    Beyond their substantial protection of individual vaccinees, it is hoped that the COVID-19 MESHD vaccines would reduce viral load in breakthrough infections MESHD thereby further suppress onward transmission. Here, analyzing positive SARS-CoV-2 test results following inoculation with the BNT162b2 mRNA vaccine, we find that the viral load is reduced 4-fold for infections occurring 12-28 days after the first dose of vaccine. These reduced viral loads hint to lower infectiousness, further contributing to vaccine impact on virus spread.

    Evolving Insights from SARS-CoV-2 Genome from 200K COVID-19 MESHD Patients

    Authors: Sanket Shashikant Desai; Aishwarya Rane; Asim Joshi; Amit Dutt

    doi:10.1101/2021.01.21.427574 Date: 2021-01-21 Source: bioRxiv

    We present an updated version of our automated computational pipeline, Infection Pathogen Detector IPD 2 HGNC.0 with a SARS-CoV-2 module, to perform genomic analysis to understand the pathogenesis and virulence of the virus. Analysing the currently available 208911 SARS-CoV2 genome sequences (as accessed on 28 Dec 2020), we generate an extensive database of sample- wise variants and clade annotation, which forms the core of the SARS-CoV-2 analysis module of the analysis pipeline. A comparative account of lineage-specific mutations in the newer SARS-CoV-2 strains emerging in the UK, South Africa and Brazil along with data reported from India identify overlapping and lineages specific acquired mutations suggesting a repetitive convergent and adaptive evolution. Thus, the persistence of pandemic may lead to the emergence of newer regional strains with improved fitness. IPD 2 HGNC.0 also adopts the recent dynamic clade nomenclature and shows improvement in accuracy of clade assignment, processing time and portability, to its predecessor and thus could be a vital tool to help facilitate genomic surveillance in a population to identify variants involved in breakthrough infections MESHD.

    Ad26.COV2.S-elicited immunity protects against G614 spike variant SARS-CoV-2 infection MESHD in Syrian hamsters and does not enhance respiratory disease in challenged animals with breakthrough infection after sub-optimal vaccine dosing

    Authors: Joan E.M. van der Lubbe; Sietske K. Rosendahl Huber; Aneesh Vijayan; Liesbeth Dekking; Ella van Huizen; Jessica Vreugdenhil; Ying Choi; Miranda R.M. Baert; Karin Feddes-de Boer; Ana Izquierdo Gil; Marjolein van Heerden; Tim J. Dalebout; Sebenzile K. Myeni; Marjolein Kikkert; Eric J. Snijder; Leon de Waal; Koert J. Stittelaar; Jeroen T.B.M. Tolboom; Jan Serroyen; Leacky Muchene; Leslie van der Fits; Lucy Rutten; Johannes P.M. Langedijk; Dan H. Barouch; Hanneke Schuitemaker; Roland C. Zahn; Frank Wegmann

    doi:10.1101/2021.01.08.425915 Date: 2021-01-08 Source: bioRxiv

    Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike PROTEIN antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection MESHD models. Here, we investigated the immunogenicity, protective efficacy and potential for vaccine-associated enhanced respiratory disease MESHD ( VAERD MESHD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 PROTEIN variant. Vaccine doses of 1x109 vp and 1x1010 vp elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection MESHD and pneumonia MESHD but not upper respiratory tract infection MESHD. A second vaccine dose further increased neutralizing antibody titers which was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease MESHD in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection MESHD. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these pre-clinical data confirm efficacy of a 1-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 PROTEIN virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.

    Vaccines that prevent SARS-CoV-2 transmission may prevent or dampen a spring wave of COVID-19 MESHD cases and deaths MESHD in 2021

    Authors: David A Swan; Ashish Goyal; Chloe Bracis; Mia Moore; Elizabeth Krantz; Elizabeth R Brown; Fabian Cardozo-Ojeda; Daniel B Reeves; Fei Gao; Peter B Gilbert; Lawrence Corey; Myron S Cohen; Holly Janes; Dobromir Dimitrov; Joshua T Schiffer

    doi:10.1101/2020.12.13.20248120 Date: 2020-12-14 Source: medRxiv

    Ongoing SARS-CoV-2 vaccine trials assess vaccine efficacy against disease (VEDIS), the ability of a vaccine to block symptomatic COVID-19 MESHD. They will only partially discriminate whether VEDIS is mediated by preventing infection as defined by the detection of virus in the airways (vaccine efficacy against infection defined as VESUSC), or by preventing symptoms despite breakthrough infection MESHD (vaccine efficacy against symptoms or VESYMP). Vaccine efficacy against infectiousness (VEINF), defined as the decrease in secondary transmissions from infected vaccine recipients versus from infected placebo recipients, is also not being measured. Using mathematical modeling of data from King County Washington, we demonstrate that if the Moderna and Pfizer vaccines, which have observed VEDIS>90%, mediate VEDIS predominately by complete protection against infection, then prevention of a fourth epidemic wave in the spring of 2021, and associated reduction of subsequent cases and deaths MESHD by 60%, is likely to occur assuming rapid enough vaccine roll out. If high VEDIS is explained primarily by reduction in symptoms, then VEINF>50% will be necessary to prevent or limit the extent of this fourth epidemic wave. The potential added benefits of high VEINF would be evident regardless of vaccine allocation strategy and would be enhanced if vaccine roll out rate is low or if available vaccines demonstrate waning immunity. Finally, we demonstrate that a 1.0 log vaccine-mediated reduction in average peak viral load might be sufficient to achieve VEINF=60% and that human challenge studies with 104 infected participants, or clinical trials in a university student population could estimate VESUSC, VESYMP and VEINF using viral load metrics.

    High Acceptance of HIV Self-testing Among PrEP Recipients before COVID-19 MESHD Era: A Cross-sectional Analysis from PrEP Demonstration Project of MSM in China

    Authors: Jing Zhang; Wei-ming Tang; Xia Jin; Hong-yi Wang; Zhen-xing Chu; Qing-hai Hu; Xiao-jie Huang; Yao-kai Chen; Hui Wang; Xiao-qing He; Yao Li; Lu-kun Zhang; Zhi-li Hu; Ran-tong Bao; Shang-cao Li; Hang Li; Hai-bo Ding; Yong-jun Jiang; Wen-qing Geng; Jun-jie Xu; Hong Shang

    doi:10.21203/rs.3.rs-36752/v1 Date: 2020-06-19 Source: ResearchSquare

    Background: Many Pre-exposure prophylaxis (PrEP) users have difficulty attending the quarterly facility-based HIV testing, which leads to the potential risk of drug resistance in the context of breakthrough infection MESHD with low drug compliance. We explored the acceptance of HIV self-testing (HIVST) service among PrEP recipients. Methods: MSM were recruited for the PrEP demonstration in four major cities in China from December 2018 to September 2019, provided with regimens of both daily and on-demand PrEP. Facility-based HIV testing was provided quarterly at clinic visits. Previous HIV testing history and acceptance of free HIVST kits to use between each quarterly clinic visit was collected. Correlates of levels of acceptance were analysed using multivariable ordinal logistic regression. Results: We recruited 1,222 MSM. among which 48.5% preferred daily PrEP and 51.5% preferred on-demand PrEP. There was 26.8% (321/1222) had never been to any facility-based HIV testing previously, and the self-reported major reason was that they had already routinely used HIVST. A quarter of the participants (74.5%, 910/1222) had used HIVST previously. There were 1184 MSM (96.9%) accepted to use HIVST between each quarterly clinic visits during PrEP usage, composing 947 ( 77.5%) very willing to, 237(19.4%)willing to, 29 (2.4%) unwilling to, and 9 (0.7%) very unwilling to. Participants preferred daily PrEP (vs. on-demand PrEP, aOR=1.8, 95% CI:1.3-2.4) and had less than 2 times of facility-based HIV testing in the past year (vs. ³2, aOR=1.4,95% CI:1.1-1.9) were more likely to have higher level of acceptance of HIVST.Conclusions: MSM had high acceptance of HIVST MESHD, especially among those preferred daily PrEP and with less facility-based HIV testing in the previous year. Offering HIVST services PrEP recipients is feasible and necessary. Above result is of great significance for promoting HIVST among PrEP users during COVID-19 MESHD, improving awareness of their HIV infection status MESHD and ensuring compliance with medication. Future study should exam the impact of HIVST on HIV testing frequency among PrEP users.Trial registration: ChiCTR1800020374 on 27th Dec 2018. http://www.chictr.org.cn/searchproj.aspx

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