Estimated reading time: 8 minutes
Seizure risks, a needle-free vaccine patch, and a compound that may limit flu replication—here are five flu stories you should check out this week.
(Click on each headline to jump to the article below.)
1) Seizure Risk Higher After COVID-19 than Influenza. People who have a COVID-19 infection are more likely to develop seizures or epilepsy within the next six months than people who have an influenza infection
2) Researchers Identify Compound That Inhibits Influenza Virus Replication. Researchers have discovered a compound that inhibits the body’s own methyltransferase MTr1, which limits the replication of influenza viruses and may lead to the development of new treatments for the flu.
3) Investigational Immune Activating Platform Boosts Influenza Vaccine Response. The preclinical research demonstrated the ability of Infectimune to significantly boost CD4 T cell activity, suggesting that Infectimune-based vaccines could provide durable protection against seasonal flu and potentially emerging pandemic flu.
4) Vaxxas Starts Clinical Trial for Needle-Free, Flu Vaccine Patch. The trial will assess the safety, tolerability, and immunogenicity of the IIV4 candidate in approximately 150 healthy participants, aged 18 to 50.
5) AAHI Awarded $9.9M to Develop Nasal Spray Influenza Vaccine. The 40-month project may culminate in a prototype bivalent vaccine candidate that is effective against both the H5N1 and H7N9 strains of influenza, according to Access to Advanced Health Institute.
Seizure Risk Higher After COVID-19 than Influenza
1) Seizure Risk Higher After COVID-19 than Influenza
People who have a COVID-19 infection are more likely to develop seizures or epilepsy within the next six months than people who have an influenza infection, according to a study published online in Neurology. The increased risk was more noticeable in children than adults. It was also more noticeable in people who did not need hospitalization for COVID-19 infections.
“While the overall risk of developing seizures or epilepsy was low—less than 1% of all people with COVID-19, given the large number of people who have been infected with COVID-19, this could result in increases in the number of people with seizures and epilepsy,” said study author Arjune Sen, MD, PhD, of the University of Oxford in England. “In addition, the increased risk of seizures and epilepsy in children gives us another reason to try to prevent COVID-19 infections in kids.”
For the study, researchers looked at a health records network for people with COVID-19 infections. A total of 152,754 patients with COVID-19 were matched to people who were diagnosed with influenza during the same time period and who were similar in age, sex and other factors, such as other medical conditions. None of the participants had previously been diagnosed with epilepsy or recurrent seizures. The researchers then looked to see whether people developed epilepsy or seizures in the following six months.
People who had COVID-19 were 55% more likely to develop epilepsy or seizures over the next six months than people who had influenza. The rate of new cases of epilepsy or seizures was 0.94% in the people who had COVID-19, compared to 0.60% in those who had influenza.
“People should interpret these results cautiously since the overall risk is low,” Sen said. “We do, however, recommend that health care professionals pay particular attention to individuals who may have more subtle features of seizures, such as focal aware seizures, where people are alert and aware of what is going on, especially in the three months following a less severe COVID-19 infection.”
A limitation of the study was that researchers were unable to identify which specific virus variants people were infected with, which could have influenced results.
Researchers Identify Compound That Inhibits Influenza Virus Replication
2) Researchers Identify Compound That Inhibits Influenza Virus Replication
Scientists have identified a compound that inhibits the body’s own methyltransferase MTr1, thereby limiting the replication of influenza viruses, according to a study from German and Japanese researchers published in the journal Science.
The team, led by Hiroki Kato, MD, from the Institute of Cardiovascular Immunology at the University Hospital Bonn, found the compound proved effective in lung tissue preparations and mouse studies and showed synergistic effects with already approved influenza drugs.
To replicate, viruses need a host cell. There they introduce their genetic information in the form of the nucleic acids DNA or RNA. These molecular blueprints are used in the host cell to produce new viruses. In order to distinguish foreign from its own nucleic acids, the cell uses a kind of labeling system. Own RNA, for example, is tagged with a molecular cap that identifies it as non-hazardous. This enables the immune system to react specifically to threats.
The molecular cap is a methylated nucleoside: a small molecule attached to the end of the RNA chain. Tagged in this way, the RNA does not trigger an immune response. However, if there is RNA in the cell that lacks the cap structure, it is recognized by the immune receptor RIG-I, and the immune system is alerted. To escape this, influenza viruses have developed a special mechanism. They steal the molecular cap from cellular RNA molecules and transfer it to their own RNA. This process is called cap-snatching.
The enzyme MTr1 provides cellular mRNA with a cap structure and thus functions as the cell’s “nucleic acid labeler.” The team now has been able to show how much influenza viruses depend on the function of the enzyme MTr1.
Investigational Immune Activating Platform Boosts Influenza Vaccine Response
3) Investigational Immune Activating Platform Boosts Influenza Vaccine Response
PDS Biotechnology’s investigational infectious disease immune activating platform, Infectimune, has shown promising results in boosting CD4 T cell responses to influenza vaccines, suggesting that Infectimune-based vaccines could provide durable protection against seasonal flu and potentially emerging pandemic flu, according to a preclinical study published in Viruses.
The studies focused on comparing Infectimune-induced immune responses following primary vaccination against influenza with immune responses induced by leading vaccine adjuvants. The paper reported findings investigating the ability of Infectimune (R-DOTAP) to promote CD4 T cell responses to vaccination with recombinant influenza protein.
Infectimune was compared to AddaVax, which is analogous to commercial adjuvant MF59, and AddaVax combined with CpG, a commercial adjuvant, using HA-B as the influenza vaccine antigen. Results from the study concluded that Infectimune dramatically enhanced CD4 T cell responses to recombinant HA-B proteins relative to AddaVax and AddaVax plus CpG.
Further, the Infectimune-elicited CD4 T cells displayed abundant interferon-gamma and interleukin-2 production that are critical for protective immunity. CD4 T cells are documented to present multiple functions, including CD8 T cell expansion and antibody responses, as well as direct anti-viral effects and potentiation of antigen-presenting function to enhance protection against viral infection.
“Influenza remains challenging due to low immune responses, especially in the elderly. Thus, there is a significant opportunity to develop a flu vaccine that induces broadly protective responses to influenza,” says Gregory Conn, PhD, PDS Biotechnology chief scientific officer, in a press release.
Vaxxas Starts Clinical Trial for Needle-Free Flu Vaccine Patch
4) Vaxxas Starts Clinical Trial for Needle-Free Flu Vaccine Patch
Clinical-stage biotechnology company Vaxxas has initiated a phase I clinical trial for the first needle-free inactivated seasonal influenza vaccine quadrivalent (IIV4) candidate, delivered using the company’s high-density microarray patch (HD-MAP) technology.
The trial will assess the safety, tolerability, and immunogenicity of the IIV4 candidate in approximately 150 healthy participants, aged 18 to 50, who have not received an influenza vaccine within the last six months and have received no vaccines for at least 30 days prior to participating in the study.
Researchers estimate that fear of needles affects up to 25% of adults and may lead to 16% of people in developed world countries skipping routine and pandemic vaccinations.
“Vaccine delivered via a HD-MAP patch is easy to use and can potentially be self-administered. It can simplify distribution by removing or reducing the need for refrigeration and avoids needles, all factors that could improve access to, and acceptability of, current influenza vaccines, offering greater protection each season to communities around the globe,” says Vaxxas CEO David L. Hoey in a press release.
In contrast to current influenza vaccines given by needle and syringe, which must be stored under refrigerated conditions, typically 2°C – 8°C to remain effective, Vaxxas has shown that influenza vaccine on the HD-MAP can be kept at temperatures up to 40°C, for at least 12 months, without losing effectiveness. These thermostability benefits of an HD-MAP influenza vaccine have the potential to enable broader distribution at a lower cost.
AAHI Awarded $9.9M to Develop Nasal Spray Influenza Vaccine
5) AAHI Awarded $9.9M to Develop Nasal Spray Influenza Vaccine
Seattle’s Access to Advanced Health Institute (AAHI) has been awarded a project agreement worth up to $9.9 million by the US government to develop a prototype intranasal bivalent influenza RNA vaccine candidate.
The vaccine will target pandemic A(H5N1) and A(H7N9) influenza virus pathogens. The 40-month project may culminate in a vaccine candidate that is effective against both strains of influenza, according to a press release by AAHI.
AAHI’s RNA platform, which delivers self-amplifying RNA bound to the exterior of a nanostructured lipid carrier, entered first-in-human clinical trials in May 2022 with phase 1/2 clinical trials of the “AAHI-SC2” COVID-19 vaccine candidate.
Current mRNA vaccines against COVID-19 reduce severe illness and hospitalization, but they require boosters to maintain protection, are not always effective against viral variants, and do not effectively curtail viral transmission. Although influenza vaccines have been available for almost a century, three influenza pandemics have occurred since the 1918 H1N1 pandemic, of which the most recent 2009 pandemic claimed hundreds of thousands of lives worldwide in the first year.
Through this award, AAHI will build on its initial research and development of an intranasal pandemic influenza RNA vaccine candidate in liquid and dry powder presentations. Intranasal vaccine administration could reduce or eliminate the use of needles by the ease of self-administration, potentially increasing vaccine uptake, and by driving key mucosal immune responses not typically induced by needle-administered vaccines.