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1.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327388

ABSTRACT

Summary SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to antibody neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-specific vaccines would enhance immunity and protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing antibody titers against D614G were 4760 and 270 reciprocal ID 50 at week 6 (peak) and week 41 (pre-boost), respectively, and 320 and 110 for Omicron. Two weeks after boost, titers against D614G and Omicron increased to 5360 and 2980, respectively, for mRNA-1273 and 2670 and 1930 for mRNA-Omicron. Following either boost, 70-80% of spike-specific B cells were cross-reactive against both WA1 and Omicron. Significant and equivalent control of virus replication in lower airways was observed following either boost. Therefore, an Omicron boost may not provide greater immunity or protection compared to a boost with the current mRNA-1273 vaccine.

2.
J Biol Chem ; 297(4): 101127, 2021 10.
Article in English | MEDLINE | ID: covidwho-1373108

ABSTRACT

The SARS-CoV-2 spike is the primary target of virus-neutralizing antibodies and critical to the development of effective vaccines against COVID-19. Here, we demonstrate that the prefusion-stabilized two-proline "S2P" spike-widely employed for laboratory work and clinical studies-unfolds when stored at 4 °C, physiological pH, as observed by electron microscopy (EM) and differential scanning calorimetry, but that its trimeric, native-like conformation can be reacquired by low pH treatment. When stored for approximately 1 week, this unfolding does not significantly alter antigenic characteristics; however, longer storage diminishes antibody binding, and month-old spike elicits virtually no neutralization in mice despite inducing high ELISA-binding titers. Cryo-EM structures reveal the folded fraction of spike to decrease with aging; however, its structure remains largely similar, although with varying mobility of the receptor-binding domain. Thus, the SARS-CoV-2 spike is susceptible to unfolding, which affects immunogenicity, highlighting the need to monitor its integrity.


Subject(s)
SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antigen-Antibody Reactions , COVID-19/pathology , COVID-19/virology , Calorimetry, Differential Scanning , Cryoelectron Microscopy , Female , Humans , Hydrogen-Ion Concentration , Mice , Mice, Inbred BALB C , Protein Structure, Tertiary , Protein Unfolding , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Time Factors
3.
Nature ; 586(7830): 567-571, 2020 10.
Article in English | MEDLINE | ID: covidwho-703377

ABSTRACT

A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the coronavirus disease 2019 (COVID-19) global pandemic. Structural studies have led to the development of mutations that stabilize Betacoronavirus spike proteins in the prefusion state, improving their expression and increasing immunogenicity1. This principle has been applied to design mRNA-1273, an mRNA vaccine that encodes a SARS-CoV-2 spike protein that is stabilized in the prefusion conformation. Here we show that mRNA-1273 induces potent neutralizing antibody responses to both wild-type (D614) and D614G mutant2 SARS-CoV-2 as well as CD8+ T cell responses, and protects against SARS-CoV-2 infection in the lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a phase III trial to evaluate its efficacy.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , Animals , Antibodies, Neutralizing/immunology , Betacoronavirus/genetics , CD8-Positive T-Lymphocytes/immunology , COVID-19 , COVID-19 Vaccines , Clinical Trials, Phase III as Topic , Coronavirus Infections/genetics , Coronavirus Infections/virology , Female , Lung/immunology , Lung/virology , Mice , Mutation , Nose/immunology , Nose/virology , Pneumonia, Viral/virology , RNA, Messenger/genetics , RNA, Viral/genetics , SARS-CoV-2 , Th1 Cells/immunology , Toll-Like Receptor 4/agonists , Toll-Like Receptor 4/immunology , Viral Vaccines/chemistry , Viral Vaccines/genetics
4.
Int J Soc Psychiatry ; 67(2): 120-127, 2021 03.
Article in English | MEDLINE | ID: covidwho-638419

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a public health emergency of international concern and poses a threat to the mental health of pregnant women. AIM: The purpose of this study was to investigate the relationship between social support and anxiety, and the mediating effect of risk perception during the COVID-19 epidemic in the third trimester pregnant women in Qingdao, China. METHODS: From 16 to 21 February 2020, an online survey was conducted, which collected the information on demographic data, anxiety, social support and risk perception to COVID-19 of women with established medical records in the ambulatory of the Department of Obstetrics at the Affiliated Hospital of Qingdao University. Anxiety was assessed by the Self-Rating Anxiety Scale (SAS), social support was assessed by the Social Support Rating Scale (SSRS) and risk perception was assessed by a self-designed questionnaire. RESULTS: This study had 308 participants with an average of 31.02 ± 3.91 years. During the period of prevention and control of the epidemic, most pregnant women adopted protective measures, such as wearing masks (97.4%), washing hands frequently (88.3%) and staying at home (76.3%). The average SAS, SSRS and risk perception scores of the participants were 42.45 ± 6.98, 44.60 ± 7.00 and 21.60 ± 5.74, respectively. The total effect of maternal social support on anxiety was -2.63 (95% confidence interval (CI): -4.40 ~ -1.44, p < .001), the direct effect was -1.44 (95% CI: -2.74 ~ -0.35, p < .05) and the indirect effect was -1.19 (95% CI: -2.49 ~ -0.51, p < .001). CONCLUSION: The third trimester pregnant women had a high level of social support, a medium level of risk perception to COVID-19 and were susceptible to anxiety. Risk perception played a mediating role between social support and anxiety.


Subject(s)
Anxiety/epidemiology , COVID-19/psychology , Pregnant Women/psychology , Social Support , Adult , COVID-19/prevention & control , China/epidemiology , Epidemics , Female , Humans , Perception , Pregnancy , Pregnancy Trimester, Third , Surveys and Questionnaires
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