A total of 33 participants who received both doses of the Moderna mRNA-1273 vaccine against SARS-CoV-2 had blood drawn over a period of 6 months after vaccination. SARS-CoV-2 neutralizing activity ...was maintained in all the patients through the entire period of follow-up. A half-life of 202 days was determined for the live-virus neutralization activity.
Purpose of review
COVID-19 represents an unprecedented public health crisis caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The antiviral remdesivir is one component of ...treating COVID-19. Unfortunately, the trials evaluating remdesivir have reported mixed results, leading to uncertainty on when to use remdesivir. This review discusses the trials evaluating the efficacy of remdesivir for COVID-19 and other supporting data to help inform the role of remdesivir in patients with COVID-19.
Recent findings
Since the start of the pandemic, there have been four randomized trials of remdesivir in treating patients hospitalized with COVID-19. More recently, extensive observational studies have provided supportive data.
Summary
The majority of trials evaluating remdesivir suggest that remdesivir is effective in the treatment of patients hospitalized with COVID-19. Although there may be a benefit in some subgroups more than others, there is insufficient data to make definitive statements about benefits or lack of benefits in particular groups. Remdesivir has demonstrated clinical benefits such as decreased time in the hospital, lower progression to mechanical ventilation, and decreased utilization of other hospital resources; it is unclear if it reduces mortality, but one randomized controlled trial suggested possible survival benefits. Based on the data available, remdesivir has been approved (or authorized for early use) in 48 countries.
The International Society for Influenza and other Respiratory Virus Diseases held its 6th Antiviral Group (isirv-AVG) conference in Rockville, Maryland, November 13–15, 2018. The three-day program ...was focused on therapeutics towards seasonal and pandemic influenza, respiratory syncytial virus, coronaviruses including MERS-CoV and SARS-CoV, human rhinovirus, and other respiratory viruses. Updates were presented on several influenza antivirals including baloxavir, CC-42344, VIS410, immunoglobulin, immune plasma, MHAA4549A, pimodivir (JNJ-63623872), umifenovir, and HA minibinders; RSV antivirals including presatovir (GS-5806), ziresovir (AK0529), lumicitabine (ALS-008176), JNJ-53718678, JNJ-64417184, and EDP-938; broad spectrum antivirals such as favipiravir, VH244, remdesivir, and EIDD-1931/EIDD-2801; and host directed strategies including nitazoxanide, eritoran, and diltiazem. Other topics included considerations of novel endpoints such as ordinal scales and patient reported outcomes (PRO), and study design issues, and other regulatory considerations for antiviral drug development. The aim of this report is to provide a summary of the presentations given at this meeting.
•Presentations given at the recent isirv-AVG conference held in Rockville, Maryland, November 13–15, 2018 are summarized.•Viruses discussed included influenza, RSV, coronavirus including MERS-CoV and others.•Therapeutics presented included polymerase inhibitors, fusion inhibitors, monoclonal antibodies, and host targets.•The challenges and strategies of conducting therapeutic studies including novel endpoints were discussed.
PURPOSE OF REVIEWThis review summarizes past and ongoing efforts for using polyclonal and monoclonal antibodies for the treatment of influenza, and is focused on products that have entered clinical ...trials.
RECENT FINDINGSAt least three polyclonal and eight monoclonal antibody products have been tested in clinical trials for the treatment of influenza. Considered across the two classes of therapeutics, these products appear to be safe and well tolerated. However, the efficacy results have been mixed and inconclusive. To date, no products have consistently shown superiority to currently available antivirals.
SUMMARYNo products within these two classes have been licensed, and several products appear to have stopped further clinical development. There are several ongoing studies that are anticipated to be completed or reported in the next 1–2 years which will be critical for understanding the value of polyclonal and monoclonal antibodies in the treatment of influenza.
In a trial of mpox vaccine, intradermal administration led to more erythema and induration than the subcutaneous route but resulted in a similar level of immune response with 20% of the dose.
Thirty-four adults received two 100-μg injections of Moderna’s mRNA SARS-CoV-2 vaccine, and serum anti–spike protein and neutralizing antibody titers were measured at day 119 — 90 days after the ...second injection. By three different assays, binding and neutralizing antibody titers declined slightly but remained elevated and higher than titers in convalescent plasma.
A severe inflammatory immune response with hypercytokinemia occurs in patients hospitalized with severe influenza, such as avian influenza A(H5N1), A(H7N9), and seasonal A(H1N1)pdm09 virus ...infections. The role of immunomodulatory therapy is unclear as there have been limited published data based on randomized controlled trials (RCTs). Passive immunotherapy such as convalescent plasma and hyperimmune globulin have some studies demonstrating benefit when administered as an adjunctive therapy for severe influenza. Triple combination of oseltamivir, clarithromycin, and naproxen for severe influenza has one study supporting its use, and confirmatory studies would be of great interest. Likewise, confirmatory studies of sirolimus without concomitant corticosteroid therapy should be explored as a research priority. Other agents with potential immunomodulating effects, including non-immune intravenous immunoglobulin, N-acetylcysteine, acute use of statins, macrolides, pamidronate, nitazoxanide, chloroquine, antiC5a antibody, interferons, human mesenchymal stromal cells, mycophenolic acid, peroxisome proliferator-activated receptors agonists, non-steroidal anti-inflammatory agents, mesalazine, herbal medicine, and the role of plasmapheresis and hemoperfusion as rescue therapy have supportive preclinical or observational clinical data, and deserve more investigation preferably by RCTs. Systemic corticosteroids administered in high dose may increase the risk of mortality and morbidity in patients with severe influenza and should not be used, while the clinical utility of low dose systemic corticosteroids requires further investigation.
•A severe inflammatory immune response with hypercytokinemia occurs in patients hospitalized with severe influenza.•Systemic corticosteroids administered in high dose may increase the risk of mortality and morbidity.•Passive immunotherapy such as convalescent plasma and hyperimmune globulin may be useful as an adjunctive therapy.•Confirmation of the efficacy of triple therapy (oseltamivir, clarithromycin, and naproxen) would be of great interest.•Other agents with immunomodulating effects deserve more investigation by randomized controlled trials.
Development of an effective vaccine against Ebola virus is of high priority. However, knowledge about potential correlates of protection and the durability of immune response after vaccination is ...limited. Here, we elucidate the human antibody repertoire after administration of vesicular stomatitis virus (VSV)-Ebola vaccine at 3 million, 20 million and 100 million plaque-forming units (PFU) and homologous VSV-Ebola vaccine boost in healthy adult volunteers. Whole genome-fragment phage display libraries, expressing linear and conformational epitopes of Ebola glycoprotein (GP), showed higher diversity of antibody epitopes in individuals vaccinated with 20 million PFU than in those vaccinated with 3 million or 100 million PFU. Surface plasmon resonance kinetics showed higher levels of GP-binding antibodies after a single vaccination with 20 million or 100 million PFU than with 3 million PFU, and these correlated strongly with neutralization titers. A second vaccination did not boost antibody or virus neutralization titers, which declined rapidly, and induced only minimal antibody affinity maturation. Isotype analysis revealed a predominant IgM response even after the second vaccination, which contributed substantially to virus neutralization in vitro. These findings may help identify new vaccine targets and aid development and evaluation of effective countermeasures against Ebola.
Neutralization of the omicron variant was assessed in serum samples obtained from persons who had received an mRNA-1273 booster. After the standard two-dose vaccine regimen, these titers were ...approximately 35 times lower than those against the D614G variant. However, boosters increased omicron neutralization by a factor of 20 — to levels that correlate with clinical resistance to infection.
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