An Australian study has shown for the first time that people with inborn errors of immunity mount some level of immune system response to covid vaccines.
Just because you can’t normally see an immune response doesn’t mean there isn’t one.
People with inborn errors of immunity experience decreased antibody production, T-cell function and/or innate immune responses. As a result, they have compromised viral clearance and immune protection, putting them at increased risk of infectious diseases such as covid.
And while it is recommended that people with IEI and other immunocompromised individuals should consider seeking a third dose of covid vaccines, how well these vaccinations protect people with IEI has not been clear.
But a new Australian-first study, published in the Journal of Allergy and Clinical Immunology, shows that IEI patients gain measurable benefits from a third covid vaccine.
Researchers compared covid immune responses of 25 adults with IEI and 29 healthcare workers after each vaccination. The first two vaccine doses were either mRNA or adenoviral vector vaccines, while all third doses were mRNA vaccines.
IEI patients were found to develop one or more kinds on adaptive immune response following the third vaccination, such as antibodies or memory B- or T-cells, although the responses were not as large as those observed in healthy adults.
Even the IEI patients who did not produce any neutralising antibodies mounted some memory B- or T-cell response, which are not detected of standard blood tests for vaccine responses.
“Although the degree of protection that this affords against severe covid is not yet known, it highlights the benefit of vaccination for these patients,” the researchers concluded.
Dr Edwards felt the results challenged long-held assumptions about how vaccines performed in immunocompromised patients while also highlighting the importance of tailoring vaccination strategies for individual patients.
“We need to look beyond antibody tests alone, to assess vaccine effectiveness,” she told media.
“In addition to measuring antibody responses, the traditional gold standard for vaccine efficacy, we also analysed the immune memory, which underpin long-term immune protection and rapid responses to future infections.
“Our research emphasises that vaccine boosters remain critical for people with immune disorders, to increase their lower protection levels.”
Proposed trial aims to increase blood testing for Alzheimer’s
The Australian Dementia Network (ADNeT) is seeking $6 million dollars in federal funding for a five-year project designed to identity and treat Alzheimer’s disease earlier and more effectively.
The proposal involves using an established network of GPs across three states to roll out a combination of digital cognitive tests and blood testing for the phosphorylated tau 217 biomarker in people at risk of developing AD.
Individuals who show signs of, or who are considered to be at risk of, AD during the pilot will be sent to brain health clinics or specialist memory clinics for further testing and treatment.
ADNeT hopes that earlier diagnosis will allow for a quicker start to treatment, ultimately delaying the onset of severe dementia and meaning AD patients can spend more time at home.
“There are currently a small number of locations in Australia using blood tests to rule out Alzheimer’s with more accurate tests expected to be available later in the year,” said ADNeT director Professor Christopher Rowe.
“This pilot brings forward the opportunity to one day have the combination of cognitive and blood testing available to Australians across the country.
“This would have transformative benefits for our society with earlier diagnosis and intervention leading to people at risk of or with early onset Alzheimer’s leading happier, more productive and fulfilling lives.
“With current wait times outside of Melbourne and Sydney for dementia diagnosis and treatment exceeding 12 months, there is a desperate need for greater support for patients.
“It also has the potential to save the Australian Government billions of dollars in healthcare costs.”
More information on the proposed trial is available via the ADNeT website.
Related
Have researchers found a safer, more effective opioid option?
Opioid analgesics, especially synthetic mu-opioid receptor (MOR) agonists, can be highly effective at providing pain relief but are associated with overdose risk. Benzimidazole opioids, more commonly known as nitazenes, are a great example of this.
Now, a new preclinical study published in Nature, has explored whether modifying etonitazene, the most potent type of nitazenes, can strike a better balance between effectiveness and potency.
Researchers have found that fluoronitrazene (FNZ), synthesised by substituting the end of etonitazine’s ethoxy chain with fluorine, and its primary metabolite N-desethyl-FNZ (DFNZ) are still highly selective for the MOR and produce potent and immediate analgesic effects in acute and chronic pain models without including respiratory depression, tolerance or MOR downregulation after repeated exposure.
“At therapeutic doses, DFNZ produced a moderate and sustained increase in brain oxygen, indicating that at this dose it did not activate MORs in respiratory nuclei. Moreover, repeated therapeutic doses of DFNZ did not produce tolerance or withdrawal effects related to metabolic, autonomic, behavioural or motor systems, and only produced a significant increase in one out of the 14 withdrawal symptoms (irritability). From the perspective of pain medication, these are strong therapeutic advantages,” the researchers wrote.
In addition, operant responding experiments suggested that DFNZ had weak reinforcement of addictive behaviours.
“We speculate that the rapid extinction of DFNZ-reinforced responding is due to its unique effects on nucleus accumbens dopamine neurotransmission and specifically its inability to induce phasic dopamine neuron activity and dopamine release,” the researchers said.
“Together, the lack of tolerance, lack of MOR density changes, weak withdrawal effects, immediate extinction of drug self-administration, lack of reinstatement and limited effects of DFNZ on NAc dopamine neurotransmission suggest that DFNZ has a low potential for abuse liability in humans.”
The results have researchers cautiously optimistic about the potential of their modified nitazenes.
“Our findings challenge the conventional dogma that high-efficacy MOR agonists are unsuitable for development as safe analgesics,” they concluded.
“Our results indicate that DFNZ, and potentially other nitazenes with similar safety profiles, warrant further investigation as potential therapeutic agents for pain. Additionally, given the favourable safety profile of DFNZ and its ability to reduce heroin self-administration, sustained-release formulations of DFNZ should be explored as novel opioid maintenance treatments.”
