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1.
Dissertation Abstracts International Section A: Humanities and Social Sciences ; 83(10-A):No Pagination Specified, 2022.
Article in English | APA PsycInfo | ID: covidwho-1990155

ABSTRACT

The purpose of this study was to explore the unique lived experiences of four middle school science teachers from North Carolina and South Carolina during and following the transition from in-person to online instruction due to the COVID-19 pandemic. Four predominant themes were identified from individual, semi-structured interviews of the teachers: technology change;organizational change;changes in curricula, delivery, and student interaction;and career and personal changes. The teachers in this study described the challenges and opportunities experienced during the rapid transition in March 2020 to virtual teaching and learning. The teachers' lived experiences seamlessly aligned with the stages of change discussed by Lewin (1947) and other researchers (Bridges & Bridges, 2017;Kotter, 2012;Lewin, 1947;Page & Schoder, 2019). The teachers' comments and experiences provided a unique perspective into the technical, personal, psychological, social, and cognitive shifts during unplanned, rapid, and disruptive change. The results of this study provided evidence of the teachers' resilience and their ability to persevere in times of crisis. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

2.
Neurol Neuroimmunol Neuroinflamm ; 9(1)2021 11.
Article in English | MEDLINE | ID: covidwho-1928234

ABSTRACT

BACKGROUND AND OBJECTIVES: A descriptive analysis of COVID-19 infection in patients with multiple sclerosis (MS) receiving fingolimod or siponimod. METHODS: We reviewed the cases of COVID-19 from postmarketing or ongoing clinical trials reported to Novartis through December 27, 2020. RESULTS: As of December 27, 2020, 283 cases had been reported in fingolimod-treated patients. The mean age was 44 years (from n = 224; range 11-69 years), and 190 were women. Of 161 cases with available information, 138 were asymptomatic (6), mild (100), or moderate (32); 50 cases required hospitalization. At the last follow-up, 140 patients were reported as recovered/recovering, condition was unchanged in 22, and deteriorated in 3 patients; 4 patients had a fatal outcome. Information was not available for 114 patients. Of the 54 cases of COVID-19 reported in siponimod-treated patients, 45 were from the postmarketing setting and 9 from an ongoing open-label clinical trial. The mean age was 54 years (from n = 45; range 31-70), and 30 were women. Of 28 cases with available information, 24 were asymptomatic (2), mild (17), or moderate (5); 9 cases required hospitalization. At the last follow-up, 27 patients were reported as recovered/recovering, condition remained unchanged for 1, and 3 patients had a fatal outcome. Information was not available for 23 patients. DISCUSSION: Based on a review of available information, the risk of more severe COVID-19 in patients receiving fingolimod or siponimod seems to be similar to that reported in the general population and the MS population with COVID-19. However, limitations of spontaneous reporting, especially missing data, should be considered in the interpretation of these observations.


Subject(s)
Azetidines/administration & dosage , Benzyl Compounds/administration & dosage , COVID-19/diagnosis , COVID-19/epidemiology , Fingolimod Hydrochloride/administration & dosage , Immunosuppressive Agents/administration & dosage , Multiple Sclerosis/drug therapy , Multiple Sclerosis/epidemiology , Adolescent , Adult , Aged , Child , Clinical Trials as Topic , Comorbidity , Female , Follow-Up Studies , Humans , Male , Middle Aged , Product Surveillance, Postmarketing , Retrospective Studies , Severity of Illness Index , Young Adult
3.
Vaccine ; 40(30): 4017-4025, 2022 06 26.
Article in English | MEDLINE | ID: covidwho-1867870

ABSTRACT

Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the coronavirus disease 2019 (COVID-19) has afflicted hundreds of millions of people in a worldwide pandemic. Several safe and effective COVID-19 vaccines are now available. However, the rapid emergence of variants and risk of viral escape from vaccine-induced immunity emphasize the need to develop broadly protective vaccines. A recombinant plant-derived virus-like particle vaccine for the ancestral COVID-19 (CoVLP) recently authorized by Canadian Health Authorities and a modified CoVLP.B1351 targeting the B.1.351 variant (both formulated with the adjuvant AS03) were assessed in homologous and heterologous prime-boost regimen in mice. Both strategies induced strong and broadly cross-reactive neutralizing antibody (NAb) responses against several Variants of Concern (VOCs), including B.1.351/Beta, B.1.1.7/Alpha, P.1/Gamma, B.1.617.2/Delta and B.1.1.529/Omicron strains. The neutralizing antibody (NAb) response was robust with both primary vaccination strategies and tended to be higher for almost all VOCs following the heterologous prime-boost regimen.


Subject(s)
COVID-19 , Vaccines, Virus-Like Particle , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Canada , Humans , Mice , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccines, Virus-Like Particle/genetics
5.
N Engl J Med ; 386(22): 2084-2096, 2022 06 02.
Article in English | MEDLINE | ID: covidwho-1830290

ABSTRACT

BACKGROUND: Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are combined with an adjuvant (Adjuvant System 03 [AS03]) to form the candidate vaccine. METHODS: In this phase 3, multinational, randomized, placebo-controlled trial conducted at 85 centers, we assigned adults (≥18 years of age) in a 1:1 ratio to receive two intramuscular injections of the CoVLP+AS03 vaccine or placebo 21 days apart. The primary objective of the trial was to determine the efficacy of the CoVLP+AS03 vaccine in preventing symptomatic coronavirus disease 2019 (Covid-19) beginning at least 7 days after the second injection, with the analysis performed after the detection of at least 160 cases. RESULTS: A total of 24,141 volunteers participated in the trial; the median age of the participants was 29 years. Covid-19 was confirmed by polymerase-chain-reaction assay in 165 participants in the intention-to-treat population; all viral samples that could be sequenced contained variants of the original strain. Vaccine efficacy was 69.5% (95% confidence interval [CI], 56.7 to 78.8) against any symptomatic Covid-19 caused by five variants that were identified by sequencing. In a post hoc analysis, vaccine efficacy was 78.8% (95% CI, 55.8 to 90.8) against moderate-to-severe disease and 74.0% (95% CI, 62.1 to 82.5) among the participants who were seronegative at baseline. No severe cases of Covid-19 occurred in the vaccine group, in which the median viral load for breakthrough cases was lower than that in the placebo group by a factor of more than 100. Solicited adverse events were mostly mild or moderate and transient and were more frequent in the vaccine group than in the placebo group; local adverse events occurred in 92.3% and 45.5% of participants, respectively, and systemic adverse events in 87.3% and 65.0%. The incidence of unsolicited adverse events was similar in the two groups up to 21 days after each dose (22.7% and 20.4%) and from day 43 through day 201 (4.2% and 4.0%). CONCLUSIONS: The CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease. (Funded by Medicago; ClinicalTrials.gov number, NCT04636697.).


Subject(s)
Adjuvants, Vaccine , COVID-19 Vaccines , COVID-19 , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/adverse effects , Adjuvants, Immunologic/therapeutic use , Adjuvants, Vaccine/administration & dosage , Adjuvants, Vaccine/adverse effects , Adjuvants, Vaccine/therapeutic use , Adult , Antibodies, Viral , COVID-19/genetics , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/therapeutic use , Double-Blind Method , Humans , Injections, Intramuscular , SARS-CoV-2/genetics , Vaccination
6.
Neurol Ther ; 11(2): 741-758, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1739456

ABSTRACT

INTRODUCTION: The SARS-CoV-2 pandemic necessitated better understanding of the impact of disease-modifying therapies on COVID-19 outcomes and vaccination. We report characteristics of COVID-19 cases and vaccination status in ofatumumab-treated relapsing multiple sclerosis (RMS) patients. METHODS: COVID-19 data analyzed were from the ongoing, open-label, long-term extension phase 3b ALITHIOS study from December 2019 (pandemic start) and post-marketing cases from August 2020 (ofatumumab first approval) up to 25 September 2021. COVID-19 cases, severity, seriousness, outcomes, vaccination status, and breakthrough infection were evaluated. RESULTS: As of 25 September 2021, 245 of 1703 patients (14.4%) enrolled in ALITHIOS receiving ofatumumab (median exposure: 2.45 years) reported COVID-19 (confirmed: 210; suspected: 35). Most COVID-19 was of mild (44.1%) or moderate (46.5%) severity, but 9% had severe/life-threatening COVID-19. There were 24 serious cases (9.8%) with 23 patients hospitalized; 22 recovered and 2 died. At study cut-off, 241 patients (98.4%) had recovered or were recovering or had recovered with sequelae and 2 (0.8%) had not recovered. Ofatumumab was temporarily interrupted in 39 (15.9%) patients. Before COVID-19 onset, IgG levels were within the normal range in all COVID-19-affected patients, while IgM was < 0.4 g/l in 23 (9.4%) patients. No patient had a reinfection. Overall, 559 patients were vaccinated (full, 476; partial, 74; unspecified, 9). Breakthrough infection was reported in 1.5% (7/476) patients, and 11 reported COVID-19 after partial vaccination. As of 25 September 2021, the Novartis Safety Database (~ 4713 patient-treatment years) recorded 90 confirmed COVID-19 cases receiving ofatumumab. Most cases were non-serious (n = 80), and ten were serious (1 medically significant, 9 hospitalized, 0 deaths). Among 36 of 90 cases with outcomes reported, 30 recovered and 6 did not recover. CONCLUSION: COVID-19 in RMS patients on ofatumumab was primarily of mild/moderate severity and non-serious in these observational data. Most recovered from COVID-19 without treatment interruption. Two people died with COVID-19. Breakthrough COVID-19 despite being fully/partially vaccinated was uncommon.

7.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327064

ABSTRACT

Background: Several COVID-19 vaccines are currently being deployed but supply constraints, concerns over durability of immune responses, solidifying vaccine hesitancy/resistance and vaccine efficacy in the face of emerging variants mean that new vaccines continue to be needed to fight the ongoing pandemic. The vaccine described here is an enveloped, coronavirus-like particle produced in plants (CoVLP) that displays the prefusion-stabilized spike (S) glycoprotein of SARS-CoV-2 (ancestral Wuhan strain) and is adjuvanted with AS03 (CoVLP+AS03). Methods: This Phase 3 randomized, observer-blind, placebo-controlled trial was conducted at 85 centers in Argentina, Brazil, Canada, Mexico, the UK, and the USA. Adults ≥18 years of age including those at high risk for COVID-19 complications were randomly assigned 1:1 to receive two intramuscular injections of CoVLP (3.75 μg) adjuvanted with AS03 or placebo, 21 days apart. The primary efficacy endpoint was prevention of symptomatic (≥ 1 symptom), PCR-confirmed SARS-CoV-2 infection with onset at least 7 days after the second injection and was triggered by the identification of ≥160 virologically-confirmed cases. Tolerability and safety of CoVLP+AS03 were also determined. Results: A total of 24,141 volunteers were randomly assigned 1:1 to receive vaccine or placebo (N= 12,074 and 12,067, respectively: median age 29, range 18 to 86 years). Overall, 83% received both doses. 14.8% were SARS-CoV-2 seropositive at baseline. Symptomatic SARS-CoV-2 infection was confirmed in 165 study participants in the intention to treat (ITT) set and 157 in the per-protocol population (PP) set. Of the 157 in the PP set, 118 COVID-19 cases were in the placebo group and 39 COVID-19 cases were in the CoVLP+AS03 group for an overall vaccine efficacy (VE) of 71.0% (95% confidence interval (CI) 58.6, 80.0). Moderate-to-severe COVID-19 occurred in 8 and 32 participants in the CoVLP+AS03 and placebo groups, respectively: VE 78.1% (95% CI: 53.9, 90.5) in the PP set overall and 84.5% (95% CI: 62.0, 94.7) in those seronegative at recruitment. To date, 100% of the sequenced strains (122/165 cases: 73.39%) were variants, dominated by Delta (45.9%) and Gamma (43.4%) strains. Vaccine efficacy by variant was 75.3% (95% CI 52.8, 87.9) against Delta and 88.6% (95% CI 74.6, 95.6) against Gamma. Cross-protection was also observed against Alpha, Lambda and Mu variants;although fewer cases were identified, all were in the placebo group. At diagnosis, viral loads in the CoVLP+AS03 breakthrough cases were >100-fold lower than in the placebo cases. Reactogenicity data for solicited adverse events (AEs) was analysed for a subset (N=4,136 in vaccine arm and N=3,683 for placebo) of participants. Reactogenicity was mostly mild to moderate, and transient, and occurred more frequently in the CoVLP+AS03 group. The safety analysis set used for unsolicited AE assessment comprised 24,076 participants who received at least one study injection: 12,036 received CoVLP+AS03 and 12,040 received placebo. All serious adverse events were assessed as unrelated, except two events reported in the same subject in the placebo group. No significant imbalance or safety concern was noted in medically attended AEs (MAAEs), adverse event of special interest (AESIs), AEs leading to withdrawal, deaths, or adverse events potentially associated with currently authorized vaccines. Conclusions: The CoVLP+AS03 vaccine candidate conferred an efficacy of 71.0% in preventing symptomatic SARS-CoV-2 infection caused by a spectrum of variants. Vaccine efficacy of 78.1% was observed against moderate and severe disease, while variant-specific efficacy ranged from 75.3% to 100%. Markedly lower viral loads in the CoVLP+AS03 group at the time of diagnosis suggests a significant virologic impact of vaccination even in the breakthrough cases. CoVLP+AS03 vaccine candidate was well tolerated, and no safety concerns were identified during the study. If approved by regulators, this more traditional protein+adjuvant vaccine produced sing the novel plant-based platform may be able to make an important contribution to the global struggle against the increasingly complex family of SARS-CoV-2 viruses (Funded by Medicago with grants from the governments of Quebec and Canada;NCT04636697 ).

8.
PLoS One ; 17(2): e0262740, 2022.
Article in English | MEDLINE | ID: covidwho-1686096

ABSTRACT

OBJECTIVES: Compare lay expectations of medical development to those of experts in the context of SARS-CoV-2 vaccine development. METHODS: A short online survey of experts and lay people measuring when participants believe important vaccine milestones would occur and how likely potential setbacks were. Samples of US and Canadian lay people recruited through Qualtrics. The expert sample was created through a contact network in vaccine development and supplemented with corresponding authors of recent scholarly review articles on vaccine development. RESULTS: In aggregate, lay people gave responses that were within 3 months of experts, tending to be later than experts for early milestones and earlier for later milestones. Median lay best estimates for when a vaccine would be available to the public were 08/2021 and 09/2021 for the US and Canadian samples, compared with 09-10/2021 for the experts. However, many individual lay responses showed more substantial disagreement with expert opinions, with 54% of lay best estimates of when a vaccine would be available to the public being before the median expert soonest estimate or after the median expert latest estimate. Lay people were much more pessimistic about vaccine development encountering setbacks than experts (median probability 59% of boxed warning compared with only 30% for experts). Misalignment between layperson and expert expectations was not explained by any demographic variables collected in our survey. CONCLUSION: Median lay expectations were generally similar to experts. At the individual level, however, lay people showed substantial variation with many believing milestones would occur much sooner than experts. Lay people were in general much more pessimistic about the prospect of setbacks than were experts.


Subject(s)
Expert Testimony , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Canada , Female , Forecasting , Humans , Male , SARS-CoV-2/isolation & purification , Surveys and Questionnaires , Time Factors , United States
9.
ACR Open Rheumatol ; 4(4): 352-362, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1638643

ABSTRACT

OBJECTIVE: Patients with rheumatic disease (RD) have an increased risk of influenza and its complications. Despite inactivated influenza vaccine (IIV) recommendations, IIV uptake in patients with RD is suboptimal, a problem of increasing importance in the COVID-19 era. We estimated the frequency of IIV hesitancy and associated factors among Canadian patients with RD. METHODS: A cross-sectional vaccine hesitancy survey was completed by rheumatology clinic patients (November 2019 to January 2020). Patients rated their likelihood of receiving the influenza vaccine (scale of 0-10). We categorized these as follows: likely to refuse (scale of 0-2), uncertain (scale of 3-7), or likely to accept (scale of 8-10). Multivariate logistical regression was used to evaluate factors associated with vaccine hesitancy. RESULTS: A total of 282 patients (63.5% of those approached) completed the survey, with 165 (58.5%) being likely to accept, 67 (23.8%) being likely to refuse, and 50 (17.7%) uncertain. Uncertain patients were younger and more likely to be employed than those in the other two groups. No previous influenza vaccination (odds ratio [OR] 36.6, 95% confidence interval [CI] 5.3-252.9), belief that vaccination should not be mandatory (OR 0.1, 95% CI 0.0-0.7), unwillingness to take time off work to be vaccinated (OR 6.8, 95% CI 1.5-30.6), and distrust in pharmaceutical companies (OR 41.0, 95% CI 5.6-301.5) predicted likeliness to refuse. Reluctance to pay for vaccination (OR 2.8, 95% CI 1.1-7.5) and no previous influenza vaccination (OR 18.9, 95% CI 3.3-109.7) predicted uncertainty. CONCLUSION: More than 40% of rheumatology patients are either likely to refuse or uncertain about receiving IIV. This contributes to suboptimal vaccine coverage in this population. Interventions addressing these concerns are needed, particularly in the COVID-19 era.

10.
Cell Mol Immunol ; 19(2): 222-233, 2022 02.
Article in English | MEDLINE | ID: covidwho-1607212

ABSTRACT

Although antivirals are important tools to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, effective vaccines are essential to control the current coronavirus disease 2019 (COVID-19) pandemic. Plant-derived virus-like particle (VLP) vaccine candidates have previously demonstrated immunogenicity and efficacy against influenza. Here, we report the immunogenicity and protection induced in rhesus macaques by intramuscular injections of a VLP bearing a SARS-CoV-2 spike protein (CoVLP) vaccine candidate formulated with or without Adjuvant System 03 (AS03) or cytidine-phospho-guanosine (CpG) 1018. Although a single dose of the unadjuvanted CoVLP vaccine candidate stimulated humoral and cell-mediated immune responses, booster immunization (at 28 days after priming) and adjuvant administration significantly improved both responses, with higher immunogenicity and protection provided by the AS03-adjuvanted CoVLP. Fifteen micrograms of CoVLP adjuvanted with AS03 induced a polyfunctional interleukin-2 (IL-2)-driven response and IL-4 expression in CD4 T cells. Animals were challenged by multiple routes (i.e., intratracheal, intranasal, and ocular) with a total viral dose of 106 plaque-forming units of SARS-CoV-2. Lower viral replication in nasal swabs and bronchoalveolar lavage fluid (BALF) as well as fewer SARS-CoV-2-infected cells and immune cell infiltrates in the lungs concomitant with reduced levels of proinflammatory cytokines and chemotactic factors in the BALF were observed in animals immunized with the CoVLP adjuvanted with AS03. No clinical, pathologic, or virologic evidence of vaccine-associated enhanced disease was observed in vaccinated animals. The CoVLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials.


Subject(s)
Adjuvants, Immunologic/adverse effects , COVID-19 Vaccines/adverse effects , COVID-19/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine/immunology , Pandemics/prevention & control , Polysorbates/adverse effects , SARS-CoV-2/immunology , Squalene/adverse effects , Tobacco/metabolism , Vaccination/methods , Vaccines, Virus-Like Particle/adverse effects , alpha-Tocopherol/adverse effects , Adjuvants, Immunologic/administration & dosage , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/epidemiology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Disease Models, Animal , Drug Combinations , Drug Compounding/methods , Immunity, Humoral , Macaca mulatta , Male , Polysorbates/administration & dosage , Recombinant Proteins/immunology , Recombinant Proteins/metabolism , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Squalene/administration & dosage , Treatment Outcome , Vaccines, Virus-Like Particle/administration & dosage , alpha-Tocopherol/administration & dosage
11.
Analyst ; 147(2): 213-222, 2022 Jan 17.
Article in English | MEDLINE | ID: covidwho-1585755

ABSTRACT

The COVID-19 pandemic demonstrated the public health benefits of reliable and accessible point-of-care (POC) diagnostic tests for viral infections. Despite the rapid development of gold-standard reverse transcription polymerase chain reaction (RT-PCR) assays for SARS-CoV-2 only weeks into the pandemic, global demand created logistical challenges that delayed access to testing for months and helped fuel the spread of COVID-19. Additionally, the extreme sensitivity of RT-PCR had a costly downside as the tests could not differentiate between patients with active infection and those who were no longer infectious but still shedding viral genomes. To address these issues for the future, we propose a novel membrane-based sensor that only detects intact virions. The sensor combines affinity and size based detection on a membrane-based sensor and does not require external power to operate or read. Specifically, the presence of intact virions, but not viral debris, fouls the membrane and triggers a macroscopically visible hydraulic switch after injection of a 40 µL sample with a pipette. The device, which we call the µSiM-DX (microfluidic device featuring a silicon membrane for diagnostics), features a biotin-coated microslit membrane with pores ∼2-3× larger than the intact virus. Streptavidin-conjugated antibody recognizing viral surface proteins are incubated with the sample for ∼1 hour prior to injection into the device, and positive/negative results are obtained within ten seconds of sample injection. Proof-of-principle tests have been performed using preparations of vaccinia virus. After optimizing slit pore sizes and porous membrane area, the fouling-based sensor exhibits 100% specificity and 97% sensitivity for vaccinia virus (n = 62). Moreover, the dynamic range of the sensor extends at least from 105.9 virions per mL to 1010.4 virions per mL covering the range of mean viral loads in symptomatic COVID-19 patients (105.6-107 RNA copies per mL). Forthcoming work will test the ability of our sensor to perform similarly in biological fluids and with SARS-CoV-2, to fully test the potential of a membrane fouling-based sensor to serve as a PCR-free alternative for POC containment efforts in the spread of infectious disease.


Subject(s)
COVID-19 , Pandemics , Humans , SARS-CoV-2 , Sensitivity and Specificity , Silicon , Virion
12.
Am J Public Health ; 111(12): 2141-2148, 2021 12.
Article in English | MEDLINE | ID: covidwho-1559282

ABSTRACT

While underscoring the need for timely, nationally representative data in ambulatory, hospital, and long-term-care settings, the COVID-19 pandemic posed many challenges to traditional methods and mechanisms of data collection. To continue generating data from health care and long-term-care providers and establishments in the midst of the COVID-19 pandemic, the National Center for Health Statistics had to modify survey operations for several of its provider-based National Health Care Surveys, including quickly adding survey questions that captured the experiences of providing care during the pandemic. With the aim of providing information that may be useful to other health care data collection systems, this article presents some key challenges that affected data collection activities for these national provider surveys, as well as the measures taken to minimize the disruption in data collection and to optimize the likelihood of disseminating quality data in a timely manner. (Am J Public Health. 2021;111(12):2141-2148. https://doi.org/10.2105/AJPH.2021.306514).


Subject(s)
COVID-19/epidemiology , Health Care Surveys/methods , Ambulatory Care/organization & administration , Data Collection/methods , Data Collection/standards , Electronic Health Records/organization & administration , Health Care Surveys/standards , Hospitalization , Humans , Long-Term Care/organization & administration , Pandemics , SARS-CoV-2 , Time Factors , United States/epidemiology
13.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294807

ABSTRACT

The rapid spread of SARS-CoV-2 continues to impact humanity on a global scale with rising total morbidity and mortality. Despite the development of several effective vaccines, new products are needed to supply ongoing demand and the needs of specific populations. We report herein a pre-specified interim analysis of the phase 2 portion of an ongoing Phase 2/3, randomized, placebo-controlled trial of a coronavirus virus-like particle (CoVLP) vaccine candidate produced in plants that displays the SARS-CoV-2 spike glycoprotein adjuvanted with AS03 ( NCT04636697 ). A total of 753 subjects were recruited between 25 November 2020 and 24 March 2021 into three groups: Healthy Adults (18-64 years: N=306), Older Adults (≥ 65 years: N=282) and Adults with Comorbidities (≥18 years: N=165) and randomized 5:1 to receive two intramuscular doses of either vaccine CoVLP (3.75 μg/dose + AS03) or placebo 21 days apart. This report presents safety, tolerability and immunogenicity data collected up to 21 days after the second dose. The immune outcomes presented include neutralizing antibody (NAb) titres and cellular (IFN-γ and IL-4 ELISpot) responses. In this study, CoVLP+AS03 was well-tolerated and adverse events (AE) after each dose were generally mild to moderate and transient. Solicited AEs in Older Adults and Adults with Comorbidities were generally less frequent than in Healthy Adults. CoVLP+AS03 induced seroconversion in >35% of subjects in each group after the first dose and in ∼98% of subjects 21 days after the second dose. In all treatment groups, NAb levels were ∼10-fold higher than those in a panel of convalescent sera. A significant minority (∼20%) of subjects had evidence of a pre-existing IFN-γ response to the S protein and almost all subjects in all groups (>88%) had detectable cellular responses (IFN-γ, IL-4 or both) at 21 days after the second dose. A Th1-biased response was most evident after the first dose and was still present after dose two. These data demonstrated that CoVLP+AS03 will likely be well-tolerated and highly immunogenic in adults ≥18 years of age with and without comorbidities.

14.
Reprod Toxicol ; 107: 69-80, 2022 01.
Article in English | MEDLINE | ID: covidwho-1531737

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the coronavirus disease 2019 (COVID-19) has afflicted tens of millions of people in a worldwide pandemic. A recently developed recombinant Plant-Derived Virus-Like Particle Vaccine candidate for COVID-19 (CoVLP) formulated with AS03 has been shown to be well-tolerated and highly immunogenic in healthy adults. Since the target population for the vaccine includes women of childbearing potential, the objective of the study was to evaluate any untoward prenatal and postnatal effects of AS03-adjuvanted CoVLP administered intramuscularly to Sprague-Dawley female rats before cohabitation for mating (22 and 8 days prior) and during gestation (Gestation Days [GD] 6 and 19). The embryo-fetal development (EFD) cohort was subjected to cesarean on GD 21 and the pre/post-natal (PPN) cohort was allowed to naturally deliver. Effects of AS03-adjuvanted CoVLP was evaluated on pregnant rats, embryo-fetal development (EFD), during parturition, lactation and the development of the F1 offspring up to weaning Vaccination with AS03-adjuvanted CoVLP induced an antibody response in F0 females and anti-SARS-CoV-2 spike-specific maternal antibodies were detected in the offspring at the end of the gestation and lactation periods. Overall, there was no evidence of untoward effects of AS03-adjuvanted CoVLP on the fertility or reproductive performance of the vaccinated F0 females. There was no evidence of untoward effects on embryo-fetal development (including teratogenicity), or early (pre-weaning) development of the F1 offspring. These results support the acceptable safety profile of the AS03-adjuvanted CoVLP vaccine for administration to women of childbearing potential.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Embryonic Development/drug effects , Fertility/drug effects , Fetal Development/drug effects , Polysorbates/administration & dosage , Squalene/administration & dosage , Vaccines, Virus-Like Particle/administration & dosage , alpha-Tocopherol/administration & dosage , Animals , Animals, Newborn , Antibodies, Viral/blood , Drug Combinations , Female , Immunoglobulin G/blood , Maternal-Fetal Exchange , Pregnancy , Rats, Sprague-Dawley , Recombinant Proteins/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Tobacco/genetics
16.
Nat Med ; 27(6): 1071-1078, 2021 06.
Article in English | MEDLINE | ID: covidwho-1233716

ABSTRACT

Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are being deployed, but the global need greatly exceeds the supply, and different formulations might be required for specific populations. Here we report Day 42 interim safety and immunogenicity data from an observer-blinded, dose escalation, randomized controlled study of a virus-like particle vaccine candidate produced in plants that displays the SARS-CoV-2 spike glycoprotein (CoVLP: NCT04450004 ). The co-primary outcomes were the short-term tolerability/safety and immunogenicity of CoVLP formulations assessed by neutralizing antibody (NAb) and cellular responses. Secondary outcomes in this ongoing study include safety and immunogenicity assessments up to 12 months after vaccination. Adults (18-55 years, n = 180) were randomized at two sites in Quebec, Canada, to receive two intramuscular doses of CoVLP (3.75 µg, 7.5 µg, and 15 µg) 21 d apart, alone or adjuvanted with AS03 or CpG1018. All formulations were well tolerated, and adverse events after vaccination were generally mild to moderate, transient and highest in the adjuvanted groups. There was no CoVLP dose effect on serum NAbs, but titers increased significantly with both adjuvants. After the second dose, NAbs in the CoVLP + AS03 groups were more than tenfold higher than titers in Coronavirus 2019 convalescent sera. Both spike protein-specific interferon-γ and interleukin-4 cellular responses were also induced. This pre-specified interim analysis supports further evaluation of the CoVLP vaccine candidate.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Drug-Related Side Effects and Adverse Reactions/prevention & control , Vaccines, Virus-Like Particle/administration & dosage , Adolescent , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/genetics , COVID-19/immunology , COVID-19/therapy , COVID-19/virology , COVID-19 Vaccines/adverse effects , Canada , Drug-Related Side Effects and Adverse Reactions/immunology , Drug-Related Side Effects and Adverse Reactions/virology , Female , Humans , Immunization, Passive , Immunogenicity, Vaccine , Male , Middle Aged , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus , Vaccines, Virus-Like Particle/adverse effects , Young Adult
17.
Vaccine ; 39(22): 3053-3066, 2021 05 21.
Article in English | MEDLINE | ID: covidwho-1096260

ABSTRACT

This is a Brighton Collaboration Case Definition of the term "Vaccine Associated Enhanced Disease" to be utilized in the evaluation of adverse events following immunization. The Case Definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2 vaccines and other emerging pathogens. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected Expert Reviewers prior to submission.


Subject(s)
COVID-19 , Vaccines , COVID-19 Vaccines , Data Collection , Humans , Immunization/adverse effects , SARS-CoV-2 , Vaccines/adverse effects
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