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Nature ; 601(7893): 410-414, 2022 01.
Article in English | MEDLINE | ID: covidwho-1521758


The CVnCoV (CureVac) mRNA vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was recently evaluated in a phase 2b/3 efficacy trial in humans1. CV2CoV is a second-generation mRNA vaccine containing non-modified nucleosides but with optimized non-coding regions and enhanced antigen expression. Here we report the results of a head-to-head comparison of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in non-human primates. We immunized 18 cynomolgus macaques with two doses of 12 µg lipid nanoparticle-formulated CVnCoV or CV2CoV or with sham (n = 6 per group). Compared with CVnCoV, CV2CoV induced substantially higher titres of binding and neutralizing antibodies, memory B cell responses and T cell responses as well as more potent neutralizing antibody responses against SARS-CoV-2 variants, including the Delta variant. Moreover, CV2CoV was found to be comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. Although CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tracts. Binding and neutralizing antibody titres were correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in non-human primates.

COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , Nucleosides/chemistry , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology , /immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/standards , Female , Macaca fascicularis/immunology , Male , Nucleosides/genetics , Respiratory System/immunology , Respiratory System/virology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Vaccines, Synthetic/standards , Viral Load , /standards
Infect Genet Evol ; 93: 104993, 2021 09.
Article in English | MEDLINE | ID: covidwho-1373190


Avian influenza virus (AIV) H7N9 that emerged in 2013 in eastern China is a novel zoonotic agent mainly circulating in poultry without clinical signs but causing severe disease with high fatality in humans in more than 5 waves. Since the emergence of highly pathogenic (HP) H7N9 variants in 2016, it has induced heavy losses in the poultry industry leading to the implementation of an intensive nationwide vaccination program at the end of wave 5 (September 2017). To characterize the ongoing evolution of H7N9 AIV, we conducted analyses of H7N9 glycoprotein genes obtained from 2013 to 2019. Bayesian analyses revealed a decreasing population size of HP H7N9 variants post wave 5. Phylogenetic topologies revealed that two novel small subclades were formed and carried several fixed amino acid mutations that were along HA and NA phylogenetic trees since wave 5. Some of the mutations were located at antigenic sites or receptor binding sites. The antigenic analysis may reveal a significant antigenic drift evaluated by hemagglutinin inhibition (HI) assay and the antigenicity of H7N9 AIV might evolute in large leaps in wave 7. Molecular simulations found that the mutations (V135T, S145P, and L226Q) around the HA receptor pocket increased the affinity to α2,3-linked sialic acid (SIA) while decreased to α2,6-linked SIA. Altered affinity may suggest that HP H7N9 variations aggravate the pathogenicity to poultry but lessen the threat to public health. Selection analyses showed that the HP H7N9 AIV experienced an increasing selection pressure since wave 5, and the national implementation of vaccination might intensify the role of natural selection during the evolution waves 6 and 7. In summary, our data provide important insights about the genetic and antigenic diversity of circulating HP H7N9 viruses from 2017 to 2019. Enhanced surveillance is urgently warranted to understand the current situation of HP H7N9 AIV.

Antigenic Variation/immunology , Birds , Genetic Variation , Influenza A Virus, H7N9 Subtype/genetics , Influenza in Birds/virology , Animals , China , Influenza A Virus, H7N9 Subtype/immunology , Phylogeny
Intern Emerg Med ; 17(2): 359-367, 2022 03.
Article in English | MEDLINE | ID: covidwho-1270539


The relationship between COVID-19 severity and viral load is unknown. Our objective was to assess the association between viral load and disease severity in COVID-19. In this single center observational study of adults with laboratory confirmed SARS-CoV-2, the first positive in-hospital nasopharyngeal swab was used to calculate the log10 copies/ml [log10 copy number (CN)] of SARS-CoV-2. Four categories based on level of care and modified sequential organ failure assessment score (mSOFA) at time of swab were determined. Median log10CN was compared between different levels of care and mSOFA quartiles. Median log10CN was compared in patients who did and did not receive influenza vaccine, and the correlation between log10CN and D-dimer was examined. We found that of 396 patients, 54.3% were male, and 25% had no major comorbidity. Hospital mortality was 15.7%. Median mSOFA was 2 (IQR 0-3). Median log10CN was 5.5 (IQR 3.3-8.0). Median log10CN was highest in non-intubated ICU patients [6.4 (IQR 4.4-8.1)] and lowest in intubated ICU patients [3.6 (IQR 2.6-6.9)] (p value < 0.01). In adjusted analyses, this difference remained significant [mean difference 1.16 (95% CI 0.18-2.14)]. There was no significant difference in log10CN between other groups in the remaining pairwise comparisons. There was no association between median log10CN and mSOFA in either unadjusted or adjusted analyses or between median log10CN in patients with and without influenza immunization. There was no correlation between log10CN and D-dimer. We conclude, in our cohort, we did not find a clear association between viral load and disease severity in COVID-19 patients. Though viral load was higher in non-intubated ICU patients than in intubated ICU patients there were no other significant differences in viral load by disease severity.

COVID-19 , Adult , Hospital Mortality , Humans , Male , SARS-CoV-2 , Severity of Illness Index , Viral Load