Archive for the ‘research’ Category

Babesia odocoilei Found in Canadian Black Legged Ticks

https://doi.org/10.3390/pathogens10030327

Detection of Babesia odocoilei in Ixodes scapularis Ticks Collected in Southern Ontario, Canada

by John D. Scott1,*, Emily L. Pascoe1, Muhammad S. Sajid1,2 and Janet E. Foley1
 
 
Pathogens 2021, 10(3), 327; https://doi.org/10.3390/pathogens10030327
Received: 5 February 2021 / Revised: 2 March 2021 / Accepted: 4 March 2021 / Published: 10 March 2021

Abstract

Tick-borne zoonotic diseases have an economic and societal impact on the well-being of people worldwide. In the present study, a high frequency of Babesia odocoilei, a red blood cell parasite, was observed in the Huronia area of Ontario, Canada. Notably, 71% (15/21) blacklegged ticks, Ixodes scapularis, collected from canine and feline hosts were infected with B. odocoilei. Consistent with U.S. studies, 12.5% (4/32) of questing I. scapularis adults collected by flagging in various parts of southwestern Ontario were positive for B. odocoilei. Our data show that all B. odocoilei strains in the present study have consistent genetic identity, and match type strains in the GenBank database. The high incidence of B. odocoilei in the Huronia area indicates that this babesial infection is established, and is cycling enzootically in the natural environment. Our data confirm that B. odocoilei has wide distribution in southern Ontario. View Full-Text
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**Comment**
 
Just last year, for the first time, Scott et al. confirmed the transstadial passage of B. odocoilei in black legged ticks molting from larvae to nymphs, showing it is present in all mobile lifestages.  These ticks are widely dispersed from common song-birds.  The question begging to be asked of course is whether Babesia odocoilei is a human pathogen.  Once again it would explain why so many aren’t testing positive for Babesia.
These important transmission studies are ignored but piling up by the week with all the newly discovered strains of coinfections that will never in a thousand years be picked up by current testing.
Transmission isn’t a sexy topic; however, and money for research continues to be driven by the climate agenda.  
 
 
 
 
 

Category:

Babesia, research, Ticks

Mapping Tick-borne Disease Risk in Wisconsin

https://www.sph.umn.edu/news/mapping-tick-borne-disease-risk-in-wisconsin/

A deer tick on a leaf.

Mapping tick-borne disease risk in Wisconsin

PhD student Austin Rau analyzed the cases of three serious — but lesser-known — tick-borne diseases in Wisconsin and found that they are increasing, moving, and varying over time across the state.

CHARLIE PLAIN | SEPTEMBER 22, 2020

Lyme disease is easily the most well-known type of tick-borne infection, but there are others that make people sick as well. Recently, a new study from the School of Public Health analyzed the cases of three other serious — but lesser-known — tick-borne diseases in Wisconsin and found that they are increasing, moving, and varying over time.

Austin Rau smiling in front of a tree.
Study lead author and PhD student Austin Rau

“Compared to Lyme disease, less research has been completed on non-Lyme tick-borne infections and awareness of these diseases is lower,” says lead author and PhD student Austin Rau. “If you ask most people, they couldn’t name what the second most-common tick-borne disease is.”

The study was published in The International Journal of Environmental Research and Public Health and was co-authored by SPH Assistant Professors Jesse Berman and Jonathan Oliver and Associate Professor Claudia Muñoz-Zanzi.

For the study, Rau and his team examined patient data from the Marshfield Clinic Healthcare System, which serves north and central Wisconsin. They analyzed patient electronic medical records for the period of 2000-2016 for clinic laboratory results confirming or supporting cases of three non-Lyme diseases from ticks: anaplasmosis, babesiosis, and ehrlichiosis. All three diseases are bacterial or parasitic infections from the bite of deer ticks and can be difficult to diagnose. In most cases, the infections produce on-going flu-like symptoms. 

Rau used his specialized training in geographical information systems and spatial analysis to map where the nearly 3,000 patients diagnosed with the diseases lived in order to determine the risk of having a positive laboratory test result in those areas.

Anaplasmosis

  • 2,728 cases of anaplasmosis were identified. 
  • People in northern Wisconsin were at greatest risk for having a positive laboratory test result.
  • The risk area for anaplasmosis shifted from west to east the study years.
  • The years of greatest risk were 2010-2016.
  • June to August were found to be peak months for positive laboratory test results, with a five times greater risk compared to other months.

Babesiosis

  • 213 cases of babesiosis were identified.
  • People in northwest Wisconsin were at greatest risk for having a positive laboratory test result.
  • The area of greatest risk was in the southern part of the clinic’s territory at the start of the study period before shifting north and then west over time.
  • The years of greatest risk were 2011-2013.
  • July to August were peak months for positive laboratory test results, raising the risk for babesiosis by seven times compared to other months.

Ehrlichiosis

  • Only 15 cases of ehrlichiosis were identified.
  • The number of cases were too small to determine any significant trends.

“It’s interesting to see that the two diseases — anaplasmosis and babesiosis — had differentgeographic patterns of risk — why is that,” asks Rau. “It could be due to a difference in infection prevalence among the ticks for these two diseases. It could also be because of the movement of ticks and animals they attach onto, such as white-tailed deer.”

According to the researchers, the behaviors of people likely are an important factor as well, and activities, such as hiking and hunting, could increase their risk of being infected by a tick.

Rau says the study’s methods and findings can help healthcare providers in Wisconsin and other regions where ticks live to determine potential hot spots and better prepare for tick season.

“It’s helpful for physicians and public health workers to know the months and geographic areas that pose the highest risk so that they can expect and be on the lookout for cases,” says Rau. “It’s also good for people to know when and where their risk of possible infection is higher so they can take appropriate measures to prevent tick bites.”

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**Comment**

Updates:

Warmer temperatures mean that adult deer ticks are now active. Be sure to start tick checks whenever you have been outside.

https://www.wiscontext.org/encountering-backyard-bloodsuckers-tick-app-tracks

**Warning** There are a number of inaccuracies within the article.

Excerpt:

With peak tick season imminent in the upper Midwest, researchers at the University of Wisconsin-Madison are hopeful more people will download and use a free smartphone app that helps track and identify the tiny blood-sucking arachnids.

The Tick App launched in Wisconsin in time for the 2018 tick season, and more than 600 people in the state have downloaded it so far. The app is part of a behavioral study being carried out by researchers at UW-Madison and Columbia University in New York who are seeking to better understand where and how people encounter ticks. They’re particularly interested in finding out what activities people are doing (and where they’re doing them) when they encounter black-legged (or deer) ticks (Ixodes scapularis), which often carry the bacterium that causes Lyme disease.

About 20-30% of deer ticks can be infected with Borrelia burgdorferi, the disease-causing bacterium, explained Lyric Bartholomay, who studies diseases in ticks and other invertebrates in the Department of Pathobiological Sciences at the UW-Madison School of Veterinary Medicine. Bartholomay spoke about the Tick App and tick-borne diseases during a May 29, 2019 interview on Wisconsin Public Radio’s The Morning Show.

For more on Wisconsin ticks.

Category:

Activism, Anaplasmosis, Babesia, Ehrlichiosis, research, Ticks

3 Lyme Arthritis Studies & How Our Immune System Can Fail to Shut Off When There’s An Infection

https://globallymealliance.org/lyme-arthritis-and-inflammation-shut-it-off/

A SUMMARY OF 3 LYME ARTHRITIS STUDIES AND HOW OUR IMMUNE SYSTEM CAN FAIL TO SHUT OFF WHEN THERE’S AN INFECTION.

by Mayla Hsu, Ph.D., Director of Research and Science, GLA

Arthritis is one of the most common symptoms of Lyme disease, commonly presenting as swelling and pain in the joints. Borrelia burgdorferi bacteria, which cause Lyme disease, migrate to the joints and create the arthritic symptoms. However, growing evidence implicates not only the bacteria, but the immune system itself as playing a key role in the disease. It’s an example of how something that should protect us can also be harmful.

Our immune system has evolved to help us get rid of pathogens like B. burgdorferi. But if it’s working like a finely tuned machine, the immune system should turn off when the job is done. Instead, research has shown multiple ways that the immune system may be failing to stop the inflammatory response after infection, thus prolonging symptoms that can be very debilitating. To study this in Lyme arthritis, synovial fluid surrounding the joints can be collected from patients. It is then analyzed for the presence of immune cells and cytokines, the chemical messengers produced by cells to help kill pathogens.

Some Lyme arthritis patients have symptoms that do not improve after antibiotic therapy, known as antibiotic-refractory Lyme arthritis. Synovial fluid from these patients has been previously studied for the presence of regulatory T cells (Tregs). These immune cells, which are a subset of specialized T cells, were counted because they act as an “off switch” for inflammation. It was suspected that one pathway to long-term Lyme arthritis may be through insufficient or malfunctioning Tregs.

In the synovial fluid of antibiotic-refractory arthritis patients, an average of 5% of activated T cells were Tregs, as compared to antibiotic-responsive arthritis patients, who had 12%. Those with fewer Tregs were less responsive to anti-rheumatic medications, their arthritis took longer to resolve, and a number of them required synovectomies, or surgical removal of inflamed joint tissues, to resolve their symptoms.

A limitation of this early study was that the amount of Tregs found in the patients before and during early B. burgdorferi infection could not be analyzed, since the patients were only identified after Lyme arthritis was well underway. Might higher pre-existing Tregs be associated with quicker recovery from arthritis? If so, the number of these cells could be used as a possible prognostic marker to help with treatment decisions.

One way to determine this would be to assess Treg cells before and after experimentally infecting animals with B. burgdorferi, since such an experiment could not be done in humans. A new study in mice used an engineered mouse strain called C57BL/6 DEREG to address this question. In these mice, Treg cells can be depleted when animals are administered minute, nontoxic doses of diphtheria toxin. This was done either before or after infecting mice, and results were compared to nondepleted mice.

The researchers found that depletion of Tregs before infection with B. burgdorferi caused earlier tibiotarsal joint swelling (day 10 after infection) than in non-depleted mice (day 16 after infection). Additionally, the Treg-depleted mice had significantly more joint swelling than control mice, and in fact, had a second wave of swelling that peaked at day 22 after infection.

The contribution of Tregs after B. burgdorferi infection was studied by depleting mice one to three weeks post-infection, and then comparing joint swelling with nondepleted mice. Although these Treg-depleted mice did have increased joint swelling compared to non-depleted animals, the difference in swelling did not achieve statistical significance and was less than in mice depleted before infection.

When the joints were examined for evidence of pathology, all of the mice whose Tregs were depleted prior to infection had lymphocyte infiltration into the joints and surrounding soft tissues, indicating the presence of immune cells homing to a site of inflammation. However, only a single mouse in the nondepleted group had a mild degree of immune cell infiltration on the surface of the joint. For mice whose Tregs were depleted one to three weeks after infection, there were no inflammatory pathological changes observed in the joint tissues.

Together, the mouse studies suggest that joint swelling and pathology were more dependent on the amount of Tregs before, rather than after infection by B. burgdorferi. But Treg function, not just abundance, may also be important. In other words, what do Tregs actually do to reduce arthritis?

Experiments that assess Treg function often focus on their ability to regulate, or suppress the proliferation of other immune cells. Tregs are also studied for their inhibition of inflammatory cytokine production. In one study of a limited number of Lyme patients, T cells, of which Tregs were a subset, were collectively cultured from the synovial fluid of either antibiotic-responsive or antibiotic-refractory arthritis patients. Tregs from the refractory patients were less able to suppress the production of inflammatory cytokines like interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) than those from the antibiotic-responsive patients.

These findings suggest that both the lower amount of Tregs, and the loss of their suppressive functions, may be why some patients have antibiotic-refractory arthritis. The study of Treg depletion in mice showed this tendency too. More studies are needed to explain how other cytokines may be involved in promoting an infection environment that ultimately, resolves or continues inflammation.

And, why some people have lower Tregs to begin with is also not yet understood – whether it is genetically determined or occurs in response to infection. But what is obvious is that the interplay between B. burgdorferi and the host immune response is complicated, depending on switches to turn inflammation on and off. More research will help us understand this regulation, and how host protection can possibly turn into harm.

RELATED BLOGS:

Lyme Arthritis: The Antibody Connection
Research POV: Lyme Arthritis and Peptidoglycan
Possible Clue to Lyme Arthritis Found in People’s Inflamed Joints

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For more:

Category:

Inflammation, Lyme, research

Focus on COVID-19 Leads to Delayed Diagnosis of Lyme Disease

https://danielcameronmd.com/covid-19-delayed-diagnosis-lyme-disease/

FOCUS ON COVID-19 LEADS TO DELAYED DIAGNOSIS OF LYME DISEASE

covid lyme disease

Hello, and welcome to another Inside Lyme Podcast. I am your host Dr. Daniel Cameron. In this episode, I’ll be discussing a unique case involving a 67-year-old man whose diagnosis of Lyme disease was delayed because clinicians suspected his symptoms were due to COVID-19.

By

The case report, by Novak and colleagues, entitled “Lyme Disease in the Era of COVID-19: A Delayed Diagnosis and Risk for Complications” was published recently in the journal Case Reports in Infectious Diseases.1

The authors report that this case “illustrates the overlap of symptoms among disparate infectious diseases and the risk of a narrow approach and focus on COVID-19 in patients with undifferentiated febrile illnesses, such as Lyme disease.”

In July 2020, the man presented with symptoms consistent with COVID-19. He had chills, body aches, fever, headache, and neck ache.

Doctors concluded he suffered from a viral-like illness and instructed him to quarantine until results from his COVID-19 test were obtained. His COVID tests were negative.

The patient’s symptoms slowly resolved without treatment.

6 weeks after symptom onset

Six weeks later, however, he developed a rash on his arm. A dermatologist diagnosed the rash as an insect bite reaction rather than Lyme disease.

However, test results for early Lyme disease were positive with 3 of 3 IgM Western blot bands. In addition, 4 of 10 IgG Western blot bands were positive.

The patient was treated with one week of doxycycline.

After 7 days of doxycycline, the man developed double vision due to sixth nerve palsy. He also suffered from headaches, neck stiffness, and new onset fatigue.

At this point, the patient was referred to a Lyme disease telemedicine referral clinic, where a diagnosis of Lyme disease was confirmed.

“This delayed diagnosis of Lyme disease in the patient we describe resulted in disseminated infection and sixth nerve palsy,” the authors write.

The patient’s spinal tap was negative. He was treated with 200 mg of doxycycline twice a day.

After 4 weeks of treatment, his sixth nerve palsy had resolved. However, he still had minimal double vision with extreme right gaze, along with difficulty initiating sleep, mild anxiety, mild daytime fatigue, and subtle, difficulty with his short-term memory.

Diagnostic issues during a pandemic

In this case, doctors focused on screening the patient for COVID-19 and recommending he quarantine. However, the man never developed COVID-19.

“They [clinicians] did not suggest further testing or give input on what could have been the cause of the chills, muscle aches, etc., ” the patient wrote. As a result, his diagnosis of Lyme disease was delayed for 6 weeks.

Novak and et al. proposed that the diagnostic delay was due to clinicians focusing solely on COVID-19 rather than examining other possible causes. Lyme disease was not considered until the patient developed an erythema migrans (EM) rash, 6 weeks after his onset of symptoms.

The man’s diagnosis was confirmed by a Lyme disease telemedicine referral clinic and he improved with treatment.

The man wrote about his frustrations with diagnostic delays even before the COVID-19 pandemic.

“I have spoken to several former business colleagues about my experience with Lyme disease. Their comments were similar; friends/family members who had Lyme disease in past years expressed the same complaint: Lyme disease was not tested for in the first stages of the illness because of the lack of a rash. Their stories were remarkably similar to mine. They experienced health problems before Lyme testing was finally considered and done.”

Editor’s perspective

The patient was left with chronic manifestations of Lyme disease. The authors did not address whether a persistent infection might be the cause of these chronic manifestations.

The following questions are addressed in this podcast episode:

  1. Was this man’s case of Lyme disease typical?
  2. Why is the author’s inclusion of “July” important?
  3. What is a 6th nerve palsy?
  4. The patient developed an EM rash 6 weeks after symptom onset. Is this unsual?
  5. The dermatologist unfortunately attributed the rash to an insect bite reaction?
  6. What is the significance of Western blot test results?
  7. Why was the spinal tap normal?
  8. Is it unusual to develop new symptoms (in this case, double vision) AFTER a week of antibiotic treatment? What would cause this?
  9. Have you seen diagnostic delays for Lyme disease patients during the COVID-19 pandemic?
  10. What are some of the causes of diagnostic delays?
  11. What are the consequences of diagnostic delays?
  12. The patient still had several symptoms following 1 month of treatment. What are your concerns regarding the remaining chronic manifestations?
  13. How has the use of telemedicine helped you in caring for your Lyme disease patients?
    • Thanks for listening to another Inside Lyme Podcast. You can read more about these cases in my show notes and on my website @DanielCameronMD.com. As always, it is your likes, comments, reviews, and shares that help spread the word about Lyme disease. Until next time on Inside Lyme.

Please remember that the advice given is general and not intended as specific advice as to any particular patient. If you require specific advice, then please seek that advice from an experienced professional.

Inside Lyme Podcast Series

This Inside Lyme case series will be discussed on my Facebook and made available on podcast and YouTube.  As always, it is your likes, comments, and shares that help spread the word about this series and our work. If you can, please leave a review on iTunes or wherever else you get your podcasts.

References:
  1. Novak CB, Scheeler VM, Aucott JN. Lyme Disease in the Era of COVID-19: A Delayed Diagnosis and Risk for Complications. Case Rep Infect Dis. 2021;2021:6699536. doi:10.1155/2021/6699536
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**Comment**
I’m too angry to write anything productive.

Category:

Lyme, research, Viruses

The EMA COVID-19 Data Leak, and What it Tells Us About mRNA Instability

https://www.bmj.com/content/372/bmj.n627

The EMA covid-19 data leak, and what it tells us about mRNA instability

BMJ 2021; 372 doi: https://doi.org/10.1136/bmj.n627 (Published 10 March 2021)Cite this as: BMJ 2021;372:n627
 
 
  1. Serena Tinari, journalist
Author affiliations
  1. serena.tinari@re-check.ch
Leaked documents show that some early commercial batches of Pfizer-BioNTech’s covid-19 vaccine had lower than expected levels of intact mRNA, prompting wider questions about how to assess this novel vaccine platform, writes Serena Tinari

As it conducted its analysis of the Pfizer-BioNTech covid-19 vaccine in December, the European Medicines Agency (EMA) was the victim of a cyberattack.1 More than 40 megabytes of classified information from the agency’s review were published on the dark web, and several journalists—including from The BMJ—and academics worldwide were sent copies of the leaks. They came from anonymous email accounts and most efforts to interact with the senders were unsuccessful. None of the senders revealed their identity, and the EMA says it is pursuing a criminal investigation.

The BMJ has reviewed the documents, which show that regulators had major concerns over unexpectedly low quantities of intact mRNA in batches of the vaccine developed for commercial production.

EMA scientists tasked with ensuring manufacturing quality—the chemistry, manufacturing, and control aspects of Pfizer’s submission to the EMA—worried about “truncated and modified mRNA species present in the finished product.” Among the many files leaked to The BMJ, an email dated 23 November by a high ranking EMA official outlined a raft of issues. In short, commercial manufacturing was not producing vaccines to the specifications expected, and regulators were unsure of the implications. EMA responded by filing two “major objections” with Pfizer, along with a host of other questions it wanted addressed.

The email identified “a significant difference in % RNA integrity/truncated species” between the clinical batches and proposed commercial batches—from around 78% to 55%. The root cause was unknown and the impact of this loss of RNA integrity on safety and efficacy of the vaccine was “yet to be defined,” the email said.

Ultimately, on 21 December, EMA authorised Pfizer-BioNTech’s vaccine. The agency’s public assessment report, a technical document published on its website, noted, “the quality of this medicinal product, submitted in the emergency context of the current (covid-19) pandemic, is considered to be sufficiently consistent and acceptable.”2

It’s unclear how the agency’s concerns were satisfied. According to one of the leaked emails dated 25 November, positive news had come from an undisclosed source in the US: “The latest lots indicate that % intact RNA are back at around 70-75%, which leaves us cautiously optimistic that additional data could address the issue,” the email said.

A near miss?

It’s also unclear whether the events in November constitute a near miss in the commercial manufacturing of mRNA vaccines.

EMA says the leaked information was partially doctored, explaining in a statement that “whilst individual emails are authentic, data from different users were selected and aggregated, screenshots from multiple folders and mailboxes have been created, and additional titles were added by the perpetrators.”3

But the documents offer the broader medical community a chance to reflect on the complexities of quality assurance for novel mRNA vaccines, which include everything from the quantification and integrity of mRNA and carrier lipids to measuring the distribution of particle sizes and encapsulation efficiency. Of particular concern is RNA instability, one of the most important variables relevant to all mRNA vaccines that has thus far received scant attention in the clinical community. It is an issue relevant not just to Pfizer-BioNTech’s vaccine but also to those produced by Moderna, CureVac, and others,4 as well as a “second generation” mRNA vaccine being pursued by Imperial College London.5

RNA instability is one of the biggest hurdles for researchers developing nucleic acid based vaccines. It is the primary reason for the technology’s stringent cold chain requirements and has been addressed by encapsulating the mRNA in lipid nanoparticles (box).

“The complete, intact mRNA molecule is essential to its potency as a vaccine,” professor of biopharmaceutics Daan J.A. Crommelin and colleagues wrote in a review article in The Journal of Pharmaceutical Sciences late last year. “Even a minor degradation reaction, anywhere along a mRNA strand, can severely slow or stop proper translation performance of that strand and thus result in the incomplete expression of the target antigen.”6

Crommelin and colleagues note that specific regulatory guidance for mRNA based vaccines has yet to be developed, and The BMJ’s attempts to clarify current standards were unsuccessful.
Transparency and confidentiality

The BMJ asked Pfizer, Moderna, and CureVac, as well as several regulators, what percentage mRNA integrity they consider acceptable for vaccines against covid-19. None offered any specifics.

The Medicines and Healthcare products Regulatory Agency, the UK’s medicines regulator, acknowledged the lack of a specified percentage RNA integrity, but declined to provide further detail. “The specification limit acceptance criteria are commercially confidential,” the agency said in an email.

The US Food and Drug Administration (FDA) directed The BMJ to read its guidance documents78 and its review of Pfizer’s vaccine,9 but none of these specify the percentage RNA the agency is requiring. Asked to comment, the regulator pointed to Pfizer:

“information that you seek that is not addressed in the FDA Review Memorandum should be directed to Pfizer.”

In subsequent correspondence, FDA, EMA, and Canadian government department Health Canada all stated that specific information related to the acceptability criteria is confidential.

EMA did acknowledge, however, that vaccine efficacy depends on the presence of suitable amounts of intact mRNA. In the case of the commercial batches that first raised alarm bells, the agency told The BMJ that the levels of truncated mRNA “and the amounts of a potential protein produced by the truncated mRNA would be too low to constitute a safety risk.” EMA did not comment on how truncated mRNA might affect efficacy. The issue was satisfactorily addressed, the agency underlined, when further information was supplied by the manufacturer.

Health Canada told The BMJ that Pfizer had conducted investigations into the root cause of reduced integrity in the commercial vaccine batches, and “changes were made in their processes to ensure that the integrity was improved and brought in line with what was seen for clinical trial batches.” Health Canada said the three agencies subsequently determined that “there was no concern with the RNA integrity or any other product specifications.”

Correspondence in the leaked documents suggests that FDA, Health Canada, and EMA were aligned on clinically qualified specifications of percentage mRNA integrity. Health Canada has confirmed to The BMJ that regulators “have worked together to align those requirements,” but all agencies declined to share with The BMJ any specifics on grounds that such information was commercially sensitive.

Pfizer also declined to comment on what percentage mRNA integrity it is aiming for, nor would it address questions about the cause of the unexpectedly low percentage mRNA integrity in certain batches, leaving open the question of whether it could happen again. Pfizer stressed: “Each batch of vaccines is tested by the official medicinal control laboratory—the Paul Ehrlich Institute in Germany—before final product release. As a result, the quality of all vaccine doses that are placed on the market in Europe has been double tested to ensure compliance with the specifications agreed upon with the regulatory authorities.”

Moderna’s chief corporate affairs officer Ray Jordan declined to respond to any of The BMJ’s questions, stating: “At this point, Moderna will not be offering additional commentary on these topics.”

CureVac, whose mRNA vaccine was submitted for EMA’s “rolling review” in February,10 told The BMJ that “it is too soon to give details.”

The shortage of information may reflect the lack of certainty, even among regulators, about how to assess the evidence fully for this novel technology. Professor Crommelin told The BMJ that, “For small, low molecular weight products, the active pharmaceutical ingredient integrity is typically close to 100%.”

But for mRNA vaccines? “Experience with mRNA integrity is limited.”

Lipid nanoparticles—where do they go and what do they do?

Conceived three decades ago, RNA based therapeutics11 have long inspired imaginations for their theoretical potential to transform cells of the body into “an on-demand drug factory.”12 But despite heavy investment by the biotech industry, bench-to-bedside translation was constantly hindered by the fragility of mRNA.

Over the years, researchers attempted to resolve intrinsic instability by encapsulating mRNA in nanocarriers made of polymers, lipids, or inorganic materials. Lipid nanoparticles (LNPs) were chosen by Moderna, Pfizer-BioNTech, CureVac, and Imperial College London for their covid-19 vaccines. This has attracted the attention of specialists in the field of pharmaceutical biotechnology, some of whom have raised concerns about further unknowns.

In a rapid response posted on bmj.com, JW Ulm, a gene therapy specialist who has published on tissue targeting of therapeutic vectors,13 raised concerns about the biodistribution of LNPs:

“At present, relatively little has been reported on the tissue localisation of the LNPs used to encase the SARS-CoV-2 spike protein-encoding messenger RNA, and it is vital to have more specific information on precisely where the liposomal nanoparticles are going after injection.”14

It is an unknown that Ulm worries could have implications for vaccine safety.

Ulm told The BMJ:

“Pfizer-BioNTech and Moderna did a remarkable job of rapidly scaling up manufacturing of such a novel system in swift fashion, which is genuinely a landmark technological achievement. However, pharmacokinetic studies, with independent laboratory confirmation, are essential to ascertain potential cytotoxicity and macroscopic toxicity, especially given the likelihood of booster injections over months or years, since the tissue trafficking patterns of the mRNA vaccine payload will determine which cells and tissues are killed by cytotoxic T-cells in each round.”

Given the variation in LNP formulations, it is unclear how relevant previous animal experiments are to answering this question.

Regulators and manufacturers contacted by The BMJ for this article did not wish to address any of the questions raised by Ulm’s rapid response.

Footnotes

  • Competing interests: I have read and understood the BMJ Group policy on declaration of interests and have no relevant interests to declare.

  • Provenance and peer review: commissioned; externally peer reviewed

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

https://bmj.com/coronavirus/usage

References

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**Comment**

For more:  

Category:

Activism, research, vaccines, Viruses