scholarly journals Comparison of Rhesus and Cynomolgus macaques as an authentic model for COVID-19

2020 ◽  
Author(s):  
Francisco J. Salguero ◽  
Andrew D. White ◽  
Gillian S. Slack ◽  
Susan A. Fotheringham ◽  
Kevin R. Bewley ◽  
...  
Keyword(s):  
Immune Responses ◽  
Lower Respiratory Tract ◽  
Human Population ◽  
Emerging Diseases ◽  
Convincing Evidence ◽  
Safety And Efficacy ◽  
Cynomolgus Macaques ◽  
Lung Histopathology ◽  
Novel Coronavirus ◽  
Study Species

ABSTRACTA novel coronavirus, SARS-CoV-2, has been identified as the causative agent of the current COVID-19 pandemic. Animal models, and in particular non-human primates, are essential to understand the pathogenesis of emerging diseases and to the safety and efficacy of novel vaccines and therapeutics. Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques, resembling the mild clinical cases of COVID-19 in humans. Immune responses against SARS-CoV-2 were also similar in both species and equivalent to those reported in milder infections and convalescent human patients. Importantly, we have devised a new method for lung histopathology scoring that will provide a metric to enable clearer decision making for this key endpoint. In contrast to prior publications, in which rhesus are accepted to be the optimal study species, we provide convincing evidence that both macaque species authentically represent mild to moderate forms of COVID-19 observed in the majority of the human population and both species should be used to evaluate the safety and efficacy of novel and repurposed interventions against SARS-CoV-2. Accessing cynomolgus macaques will greatly alleviate the pressures on current rhesus stocks.

scholarly journals Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Francisco J. Salguero ◽  
Andrew D. White ◽  
Gillian S. Slack ◽  
Susan A. Fotheringham ◽  
Kevin R. Bewley ◽  
...  
Keyword(s):  
Emerging Diseases ◽  
Convincing Evidence ◽  
Transcriptional Analysis ◽  
Infection Model ◽  
Global Response ◽  
Safety And Efficacy ◽  
Cynomolgus Macaques ◽  
Lung Histopathology ◽  
Novel Coronavirus ◽  
Study Species

AbstractA novel coronavirus, SARS-CoV-2, has been identified as the causative agent of the current COVID-19 pandemic. Animal models, and in particular non-human primates, are essential to understand the pathogenesis of emerging diseases and to assess the safety and efficacy of novel vaccines and therapeutics. Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques. Immune responses against SARS-CoV-2 are also similar in both species and equivalent to those reported in milder infections and convalescent human patients. This finding is reiterated by our transcriptional analysis of respiratory samples revealing the global response to infection. We describe a new method for lung histopathology scoring that will provide a metric to enable clearer decision making for this key endpoint. In contrast to prior publications, in which rhesus are accepted to be the preferred study species, we provide convincing evidence that both macaque species authentically represent mild to moderate forms of COVID-19 observed in the majority of the human population and both species should be used to evaluate the safety and efficacy of interventions against SARS-CoV-2. Importantly, accessing cynomolgus macaques will greatly alleviate the pressures on current rhesus stocks.

Chitosan alters inactivated respiratory syncytial virus vaccine elicited immune responses without affecting lung histopathology in mice

Vaccine ◽  
2019 ◽  
Vol 37 (30) ◽  
pp. 4031-4039 ◽  
Author(s):  
Abenaya Muralidharan ◽  
Marsha S. Russell ◽  
Louise Larocque ◽  
Caroline Gravel ◽  
Simon Sauvé ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Virus Vaccine ◽  
Lung Histopathology ◽  
Syncytial Virus ◽  
Respiratory Syncytial Virus Vaccine

scholarly journals Artificial intelligence predicts the immunogenic landscape of SARS-CoV-2 leading to universal blueprints for vaccine designs

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Brandon Malone ◽  
Boris Simovski ◽  
Clément Moliné ◽  
Jun Cheng ◽  
Marius Gheorghe ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Monte Carlo ◽  
Cell Surface ◽  
Antigen Presentation ◽  
Human Population ◽  
Host Immune System ◽  
T Cell Epitopes ◽  
Digital Twin ◽  
Novel Coronavirus ◽  
Global Population

AbstractThe global population is at present suffering from a pandemic of Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The goal of this study was to use artificial intelligence (AI) to predict blueprints for designing universal vaccines against SARS-CoV-2, that contain a sufficiently broad repertoire of T-cell epitopes capable of providing coverage and protection across the global population. To help achieve these aims, we profiled the entire SARS-CoV-2 proteome across the most frequent 100 HLA-A, HLA-B and HLA-DR alleles in the human population, using host-infected cell surface antigen presentation and immunogenicity predictors from the NEC Immune Profiler suite of tools, and generated comprehensive epitope maps. We then used these epitope maps as input for a Monte Carlo simulation designed to identify statistically significant “epitope hotspot” regions in the virus that are most likely to be immunogenic across a broad spectrum of HLA types. We then removed epitope hotspots that shared significant homology with proteins in the human proteome to reduce the chance of inducing off-target autoimmune responses. We also analyzed the antigen presentation and immunogenic landscape of all the nonsynonymous mutations across 3,400 different sequences of the virus, to identify a trend whereby SARS-COV-2 mutations are predicted to have reduced potential to be presented by host-infected cells, and consequently detected by the host immune system. A sequence conservation analysis then removed epitope hotspots that occurred in less-conserved regions of the viral proteome. Finally, we used a database of the HLA haplotypes of approximately 22,000 individuals to develop a “digital twin” type simulation to model how effective different combinations of hotspots would work in a diverse human population; the approach identified an optimal constellation of epitope hotspots that could provide maximum coverage in the global population. By combining the antigen presentation to the infected-host cell surface and immunogenicity predictions of the NEC Immune Profiler with a robust Monte Carlo and digital twin simulation, we have profiled the entire SARS-CoV-2 proteome and identified a subset of epitope hotspots that could be harnessed in a vaccine formulation to provide a broad coverage across the global population.

scholarly journals Candidate targets for immune responses to 2019-Novel Coronavirus (nCoV): sequence homology- and bioinformatic-based predictions

2020 ◽  
Author(s):  
Alba Grifoni ◽  
John Sidney ◽  
Yun Zhang ◽  
Richard H Scheuermann ◽  
Bjoern Peters ◽  
...  
Keyword(s):  
Immune Responses ◽  
Sequence Similarity ◽  
Rapid Expansion ◽  
Immune Recognition ◽  
T Cell Epitopes ◽  
High Sequence Similarity ◽  
Essential Information ◽  
Viral Spread ◽  
Recent Emergence ◽  
Novel Coronavirus

ABSTRACTEffective countermeasures against the recent emergence and rapid expansion of the 2019-Novel Coronavirus (2019-nCoV) require the development of data and tools to understand and monitor viral spread and immune responses. However, little information about the targets of immune responses to 2019-nCoV is available. We used the Immune Epitope Database and Analysis Resource (IEDB) resource to catalog available data related to other coronaviruses, including SARS-CoV, which has high sequence similarity to 2019-nCoV, and is the best-characterized coronavirus in terms of epitope responses. We identified multiple specific regions in 2019-nCoV that have high homology to SARS virus. Parallel bionformatic predictions identified a priori potential B and T cell epitopes for 2019-nCoV. The independent identification of the same regions using two approaches reflects the high probability that these regions are targets for immune recognition of 2019-nCoV.ONE SENTENCE SUMMARYWe identified potential targets for immune responses to 2019-nCoV and provide essential information for understanding human immune responses to this virus and evaluation of diagnostic and vaccine candidates.

scholarly journals Broadly Reactive H2 Hemagglutinin Vaccines Elicit Cross-Reactive Antibodies in Ferrets Preimmune to Seasonal Influenza A Viruses

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Z. Beau Reneer ◽  
Amanda L. Skarlupka ◽  
Parker J. Jamieson ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Recombinant Proteins ◽  
Human Population ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Wild Type ◽  
Influenza A Viruses ◽  
Global Pandemic

ABSTRACT Influenza vaccines have traditionally been tested in naive mice and ferrets. However, humans are first exposed to influenza viruses within the first few years of their lives. Therefore, there is a pressing need to test influenza virus vaccines in animal models that have been previously exposed to influenza viruses before being vaccinated. In this study, previously described H2 computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) vaccines (Z1 and Z5) were tested in influenza virus “preimmune” ferret models. Ferrets were infected with historical, seasonal influenza viruses to establish preimmunity. These preimmune ferrets were then vaccinated with either COBRA H2 HA recombinant proteins or wild-type H2 HA recombinant proteins in a prime-boost regimen. A set of naive preimmune or nonpreimmune ferrets were also vaccinated to control for the effects of the multiple different preimmunities. All of the ferrets were then challenged with a swine H2N3 influenza virus. Ferrets with preexisting immune responses influenced recombinant H2 HA-elicited antibodies following vaccination, as measured by hemagglutination inhibition (HAI) and classical neutralization assays. Having both H3N2 and H1N1 immunological memory regardless of the order of exposure significantly decreased viral nasal wash titers and completely protected all ferrets from both morbidity and mortality, including the mock-vaccinated ferrets in the group. While the vast majority of the preimmune ferrets were protected from both morbidity and mortality across all of the different preimmunities, the Z1 COBRA HA-vaccinated ferrets had significantly higher antibody titers and recognized the highest number of H2 influenza viruses in a classical neutralization assay compared to the other H2 HA vaccines. IMPORTANCE H1N1 and H3N2 influenza viruses have cocirculated in the human population since 1977. Nearly every human alive today has antibodies and memory B and T cells against these two subtypes of influenza viruses. H2N2 influenza viruses caused the 1957 global pandemic and people born after 1968 have never been exposed to H2 influenza viruses. It is quite likely that a future H2 influenza virus could transmit within the human population and start a new global pandemic, since the majority of people alive today are immunologically naive to viruses of this subtype. Therefore, an effective vaccine for H2 influenza viruses should be tested in an animal model with previous exposure to influenza viruses that have circulated in humans. Ferrets were infected with historical influenza A viruses to more accurately mimic the immune responses in people who have preexisting immune responses to seasonal influenza viruses. In this study, preimmune ferrets were vaccinated with wild-type (WT) and COBRA H2 recombinant HA proteins in order to examine the effects that preexisting immunity to seasonal human influenza viruses have on the elicitation of broadly cross-reactive antibodies from heterologous vaccination.

scholarly journals A clinical, laboratory, radiological, and microbiologicalstudy of pneumonia associated with covid-19 indicating person-to-person transmission

2021 ◽  
pp. 43832-43834
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Clinical Laboratory ◽  
Family Members ◽  
Rt Pcr ◽  
Geographical Regions ◽  
The Family ◽  
Nextgeneration Sequencing ◽  
Novel Coronavirus

Background: Novel coronavirus outbreak that originated in Wuhan, province of China has now been declared as one of the deadliest pandemics inflicting humankind in last hundred years. Method: In the present study, we have inferred the clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after coming back from overseas and touchdown right here in India on 1st March 2020 earlier than lockdown and another member of the family who didn’tvisit thiscountry. Results: From March 10, 2020, we enrolled a family of six patients who travelled to SingaporeonJanuary 10th 2020and returned on March 1st 2020. Of six family members who travelled to Singapore, five were recognised as affected with the radical coronavirus (COVID 19). Additionally, one family member, who did not travel to overseas also became infected with the virus post14 days of staying with four of the family members. Five family members (aged 30–55 years) presented with symptoms like fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3–6 days after exposure. Phylogenetic evaluation of these five subjects’ RT-PCR amplicons and two full genomes by nextgeneration sequencing presented that this is a novel coronavirus, which is closest to the severe acute respiratory syndrome (SARS)-related coronaviruses. Conclusion: Our findings are steady with person-to-person transmission of this novel coronavirus in hospital (nosocomial) and family settings, and the reports of infected travellers in other geographical regions.

scholarly journals Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs

npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Maria Blasi ◽  
Donatella Negri ◽  
Kevin O. Saunders ◽  
Erich J. Baker ◽  
Hannah Stadtler ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Lentiviral Vector ◽  
Rhesus Macaques ◽  
Infected Individual ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Safety And Efficacy ◽  
Env Protein ◽  
Hiv 1

AbstractA preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactive neutralizing antibodies (bnAbs). One strategy to achieve this goal is to define envelope (Env) evolution that drives bnAb development in infection and to recreate those events by vaccination. In this study, we report the immunogenicity, safety, and efficacy in rhesus macaques of an SIV-based integrase defective lentiviral vector (IDLV) expressing sequential gp140 Env immunogens derived from the CH505 HIV-1-infected individual who made the CH103 and CH235 bnAb lineages. Immunization with IDLV expressing sequential CH505 Envs induced higher magnitude and more durable binding and neutralizing antibody responses compared to protein or DNA +/− protein immunizations using the same sequential envelopes. Compared to monkeys immunized with a vector expressing Envs alone, those immunized with the combination of IDLV expressing Env and CH505 Env protein demonstrated improved durability of antibody responses at six months after the last immunization as well as lower peak viremia and better virus control following autologous SHIV-CH505 challenge. There was no evidence of vector mobilization or recombination in the immunized and challenged monkeys. Although the tested vaccines failed to induce bnAbs and to mediate significant protection following SHIV-challenge, our results show that IDLV proved safe and successful at inducing higher titer and more durable immune responses compared to other vaccine platforms.

scholarly journals Vaccine Protection against Multidrug-Resistant Klebsiella pneumoniae in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Natalia Malachowa ◽  
Scott D. Kobayashi ◽  
Adeline R. Porter ◽  
Brett Freedman ◽  
Patrick W. Hanley ◽  
...  
Keyword(s):  
United States ◽  
Risk Factors ◽  
Health Care ◽  
Lower Respiratory Tract ◽  
The United States ◽  
Multidrug Resistant ◽  
Sequence Type ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Cynomolgus Macaques

ABSTRACT Klebsiella pneumoniae is a human gut communal organism and notorious opportunistic pathogen. The relative high burden of asymptomatic colonization by K. pneumoniae is often compounded by multidrug resistance—a potential problem for individuals with significant comorbidities or other risk factors for infection. A carbapenem-resistant K. pneumoniae strain classified as multilocus sequence type 258 (ST258) is widespread in the United States and is usually multidrug resistant. Thus, treatment of ST258 infections is often difficult. Inasmuch as new preventive and/or therapeutic measures are needed for treatment of such infections, we developed an ST258 pneumonia model in cynomolgus macaques and tested the ability of an ST258 capsule polysaccharide type 2 (CPS2) vaccine to moderate disease severity. Compared with sham-vaccinated animals, those vaccinated with ST258 CPS2 had significantly less disease as assessed by radiography 24 h after intrabronchial installation of 108 CFU of ST258. All macaques vaccinated with CPS2 ultimately developed ST258-specific antibodies that significantly enhanced serum bactericidal activity and killing of ST258 by macaque neutrophils ex vivo. Consistent with a protective immune response to CPS2, transcripts encoding inflammatory mediators were increased in infected lung tissues obtained from CPS-vaccinated animals compared with control, sham-vaccinated macaques. Taken together, our data provide support for the idea that vaccination with ST258 CPS can be used to prevent or moderate infections caused by ST258. As with studies performed decades earlier, we propose that this prime-boost vaccination approach can be extended to include multiple capsule types. IMPORTANCE Multidrug-resistant bacteria continue to be a major problem worldwide, especially among individuals with significant comorbidities and other risk factors for infection. K. pneumoniae is among the leading causes of health care-associated infections, and the organism is often resistant to multiple classes of antibiotics. A carbapenem-resistant K. pneumoniae strain known as multilocus sequence type 258 (ST258) is the predominant carbapenem-resistant Enterobacteriaceae in the health care setting in the United States. Infections caused by ST258 are often difficult to treat and new prophylactic measures and therapeutic approaches are needed. To that end, we developed a lower respiratory tract infection model in cynomolgus macaques in which to test the ability of ST258 CPS to protect against severe ST258 infection.

Sign in / Sign up

Export Citation Format

Share Document