Two injections of mRNA-1273, a lipid nanoparticle–encapsulated mRNA-based vaccine produced in collaboration with the NIAID that encodes the SARS-CoV-2 spike protein, conferred protection against ...Covid-19 illness in 94% of vaccinated patients. Adverse effects of the vaccine were mild, transient local reactions, and the incidence of systemic effects such as fever, headache, and fatigue was low.
mRNA vaccines against respiratory viruses Whitaker, Jennifer A; Sahly, Hana M El; Healy, C Mary
Current opinion in infectious diseases,
10/2023, Letnik:
36, Številka:
5
Journal Article
Recenzirano
The successes of the coronavirus disease 2019 (COVID-19) mRNA vaccines have accelerated the development of mRNA vaccines against other respiratory pathogens. The aim of this review is to highlight ...COVID-19 mRNA vaccine advances and provide an update on the progress of mRNA vaccine development against other respiratory pathogens.
The COVID-19 mRNA vaccines demonstrated effectiveness in preventing severe COVID-19 and death. H7N9 and H10N8 avian influenza mRNA vaccines have demonstrated safety and immunogenicity in phase 1 clinical trials. Numerous seasonal influenza mRNA vaccines are in phase 1-3 clinical trials. Respiratory syncytial virus (RSV) mRNA vaccines have progressed to phase 2-3 clinical trials in adults and a phase 1 clinical trial in children. A combined human metapneumovirus and parainfluenza-3 mRNA vaccines was found to be well tolerated and immunogenic in a phase 1 trial among adults and trials are being conducted among children. Clinical trials of mRNA vaccines combining antigens from multiple respiratory viruses are underway.
The development of mRNA vaccines against respiratory viruses has progressed rapidly in recent years. Promising vaccine candidates are moving through the clinical development pathway to test their efficacy in preventing disease against respiratory viral pathogens.
Immunoassays for determining past SARS-CoV-2 infection have not been systematically evaluated in vaccinated persons in comparison with unvaccinated persons.
To evaluate antinucleocapsid antibody ...(anti-N Ab) seropositivity in mRNA-1273 (Moderna) vaccinees with breakthrough SARS-CoV-2 infection.
Nested substudy of a phase 3 randomized, double-blind, placebo-controlled vaccine efficacy trial. (ClinicalTrials.gov: NCT04470427).
99 sites in the United States, July 2020 through March 2021.
Participants were aged 18 years or older, had no known history of SARS-CoV-2 infection, and were at risk for SARS-CoV-2 infection or severe COVID-19. Substudy participants were diagnosed with SARS-CoV-2 infection during the trial's blinded phase.
2 mRNA-1273 or placebo injections 28 days apart.
Nasopharyngeal swabs from days 1 and 29 (vaccination days) and from symptom-prompted illness visits were tested for SARS-CoV-2 via polymerase chain reaction (PCR). Serum samples from days 1, 29, and 57 and the participant decision visit (PDV, when participants were informed of treatment assignment; median day 149) were tested for anti-N Abs by the Elecsys immunoassay.
Among 812 participants with PCR-confirmed COVID-19 illness during the blinded phase of the trial (through March 2021), seroconversion to anti-N Abs (median of 53 days after diagnosis) occurred in 21 of 52 mRNA-1273 vaccinees (40% 95% CI, 27% to 54%) versus 605 of 648 placebo recipients (93% CI, 92% to 95%). Each 1-log increase in SARS-CoV-2 viral copies at diagnosis was associated with 90% higher odds of anti-N Ab seroconversion (odds ratio, 1.90 CI, 1.59 to 2.28).
The scope was restricted to mRNA-1273 vaccinees and the Elecsys assay, the sample size was small, data on Delta and Omicron infections were lacking, and the analysis did not address a prespecified objective of the trial.
Vaccination status should be considered when interpreting seroprevalence and seropositivity data based solely on anti-N Ab testing.
National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
The mRNA-1273 vaccine for coronavirus disease 2019 (COVID-19) demonstrated 93.2% efficacy in reduction of symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the ...blinded portion of the Phase 3 Coronavirus Efficacy (COVE) trial. While mRNA-1273 demonstrated high efficacy in prevention of COVID-19, including severe disease, its effect on the viral dynamics of SARS-CoV-2 infections is not understood. Here, in exploratory analyses, we assessed the impact of mRNA-1273 vaccination in the ongoing COVE trial (number NCT04470427) on SARS-CoV-2 copy number and shedding, burden of disease and infection, and viral variants. Viral variants were sequenced in all COVID-19 and adjudicated COVID-19 cases (n = 832), from July 2020 in the blinded part A of the study to May 2021 of the open-label part B of the study, in which participants in the placebo arm started to receive the mRNA-1273 vaccine after US Food and Drug Administration emergency use authorization of mRNA-1273 in December 2020. mRNA-1273 vaccination significantly reduced SARS-CoV-2 viral copy number (95% confidence interval) by 100-fold on the day of diagnosis compared with placebo (4.1 (3.4-4.8) versus 6.2 (6.0-6.4) log
copies per ml). Median times to undetectable viral copies were 4 days for mRNA-1273 and 7 days for placebo. Vaccination also substantially reduced the burden of disease and infection scores. Vaccine efficacies (95% confidence interval) against SARS-CoV-2 variants circulating in the United States during the trial assessed in this post hoc analysis were 82.4% (40.4-94.8%) for variants Epsilon and Gamma and 81.2% (36.1-94.5%) for Epsilon. The detection of other, non-SARS-CoV-2, respiratory viruses during the trial was similar between groups. While additional study is needed, these data show that in SARS-CoV-2-infected individuals, vaccination reduced both the viral copy number and duration of detectable viral RNA, which may be markers for the risk of virus transmission.
Abstract
As the coronavirus disease 2019 (COVID-19) pandemic has progressed, a large volume of literature has developed delineating the clinical manifestations of acute infection. Recent reports have ...also started to describe persistent symptoms extending beyond the period of initial illness or hospitalization. Anecdotes of different signs and symptoms occurring after acute infection have also arisen in the lay press. Here we describe the current existing medical literature on the emerging concept of postacute COVID-19 and suggest an approach to classifying different manifestations of the syndrome. We also review long-term clinical manifestations observed in patients who recovered from infection due to other epidemic coronaviruses and briefly discuss potential mechanisms driving the phenomenon of postacute COVID-19.
In a trial involving 1033 patients hospitalized with Covid-19, the addition of baricitinib to remdesivir was associated with shorter recovery time, particularly among patients receiving high-flow ...oxygen, and with a 30% higher odds of improvement at day 15 than remdesivir alone. Adverse events were less frequent with the combination therapy.
Patients infected with HIV remain at increased risk of mortality and morbidity from diseases that are preventable with vaccines partly due to the persisting immunopathology that results in impaired ...responses to vaccination despite virologic suppression. Because data on clinical effectiveness in patients who are immunocompromised remain limited, undervaccination of individuals with HIV poses a major concern. Multiple societies have published recommendations on vaccination in individuals infected with HIV. Many of these recommendations are based on extrapolation of data from clinical trials that usually exclude patients with HIV, although there is a growing body of data from patients infected with HIV as well. In this review, we describe the available literature on vaccine response in the adult patient with HIV as measured by immunogenicity or vaccine efficacy.
In the coronavirus efficacy (COVE) phase 3 clinical trial, vaccine recipients were assessed for neutralizing and binding antibodies as correlates of risk for COVID-19 disease and as correlates of ...protection. These immune markers were measured at the time of second vaccination and 4 weeks later, with values reported in standardized World Health Organization international units. All markers were inversely associated with COVID-19 risk and directly associated with vaccine efficacy. Vaccine recipients with postvaccination 50% neutralization titers 10, 100, and 1000 had estimated vaccine efficacies of 78% (95% confidence interval, 54 to 89%), 91% (87 to 94%), and 96% (94 to 98%), respectively. These results help define immune marker correlates of protection and may guide approval decisions for messenger RNA (mRNA) COVID-19 vaccines and other COVID-19 vaccines.
The mRNA-1273 vaccine was approved for emergency use in December 2020; trial participants who received placebo were informed of the results and offered vaccination. At the close of the blinded phase ...of the trial, the vaccine efficacy in preventing Covid-19 illness was 93.2%, and the efficacy against severe disease was 98.2%. No new safety issues were identified.
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