Fungal vaccine developments
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The numbers of people at risk of fungal infections are increasing due to an aging population, increased use of immunosuppressive medications, pre-existing medical conditions, environmental changes, and lifestyle factors. Therefore, there is a growing need for new treatments or preventative options.
Current treatment options for fungal infections often involve the use of antifungal medications, such as azoles, echinocandins, and polyenes. These medications are generally effective in treating fungal infections, but they can have drawbacks. For example, some antifungal drugs can interact with other medications, leading to potentially harmful side effects. Additionally, overuse of antifungal drugs can contribute to the development of antifungal drug resistance, which can make treatment more challenging.
There has been a growing interest in the development of fungal vaccines as an alternative treatment. A fungal vaccine works by stimulating the immune system to produce a specific response against the fungus, which can provide long-term protection against infection. The vaccine could be given to at-risk individuals before exposure to the fungus, preventing infection from occurring in the first place.
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A recent study by researchers from the University of Georgia demonstrated the potential for a pan-fungal vaccine to protect against multiple fungal pathogens, including those that cause aspergillosis, candidiasis, and pneumocystosis. The vaccine, called NXT-2, was designed to stimulate the immune system to recognize and fight against several types of fungi.
The study found that the vaccine was able to induce a strong immune response in mice and additionally protect them from infection with several different fungal pathogens, including Aspergillus fumigatus, which is the main cause of aspergillosis. The vaccine was found to be safe and well-tolerated in the mice, with no adverse effects reported.
This study demonstrates the potential for a pan-fungal vaccine to protect against multiple fungal pathogens. While the study did not specifically address the use of the vaccine in patients with pre-existing aspergillosis infections, the findings suggest that the vaccine has potential to prevent aspergillosis infection in high-risk individuals.
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In summary, while the development of antifungal vaccines offers a promising potential alternative to the challenges posed by current treatment options for fungal infections, further research is needed to determine the safety and efficacy of the vaccine in humans, including those with aspergillosis, before it can be considered as a treatment option.
Original paper: https://academic.oup.com/pnasnexus/article/1/5/pgac248/6798391?login=false
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Spring COVID Booster
COVID-19 levels of infection in the UK are far lower than they have been earlier in the pandemic, even while most people have returned to taking fewer precautions against infection. Increased immunity in the UK population caused by vaccination and infection has likely brought us to this better place.
However levels of immunity are not fixed and much like the common cold it gradually declines in each of us, leaving us open to re-infection within a year. Consequently, we must keep 'topping up' immunity in order to avoid severe symptoms should we be infected. For most of us that are now likely to be a natural process of periodic re-infection until the virus stops circulating so widely.
If you are in a highly vulnerable group it is safest to top-up your immunity without being infected by having a booster vaccination. The Uk government will launch a spring booster campaign shortly to address this need.
Those who will be offered this booster will only be the most at risk, so you may or may not be offered it depending on the opinion of your local hospital doctor or GP. The criteria for the spring booster seem to be more restricted than earlier boosters and will only be offered 6 months after your last booster.
Criteria for the spring campaign are:
- adults aged 75 years and over
- residents in a care home for older adults
- individuals aged 5 years and over who are immunosuppressed (Your doctor will get guidelines to decide this for you)
There will likely be a less restricted booster jab in autumn 2023 too.
Vaccine Types
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Vaccines. Something most, if not all of us, are familiar with. MMR (Measles, Mumps & Rubella), TB (Tuberculosis), Smallpox, Chicken Pox, and the more recent HPV (Human Papillomavirus) and Covid-19 vaccines are just a few of the many available to protect us from harmful pathogens (an organism that causes disease like bacteria or viruses – aka 'germs'). But what exactly is a vaccine, and how does it protect us?
Firstly, to understand vaccines, it helps to have a fundamental understanding of the immune system. The immune system is the body's natural defence against harmful pathogens. It is a complex system of organs and cells that work together to help fight off infection caused by invading pathogens. When a 'germ' enters our body, the immune system triggers a series of responses to identify and destroy it.
Outward signs we are having an immune response are:
- A raised temperature (fever) and uncontrollable shivering (Rigors).
- Inflammation; this can be internal or visible on the skin's surface – for example, from a cut.
- Coughing & Sneezing (mucus traps germs, which are then removed by the action of coughing or sneezing).
Types of immunity:
Innate (also called nonspecific or natural) immunity: We are born with a combination of physical (skin and mucous membranes in the respiratory and gastrointestinal tracts), chemical (for example, stomach acid, mucous, saliva and tears contain enzymes that breakdown the cell wall of many bacteria1), and cellular (natural killer cells, macrophages, eosinophils are just a few2) defences against pathogens. Innate immunity is a type of general protection designed to immediately respond to the presence of a pathogen.
Adaptive immunity: The adaptive, or acquired, immune response is more specific to an invading pathogen and occurs after exposure to an antigen (a toxin or foreign substance which induces an immune response) either from a pathogen or vaccination.3
Below is an excellent video from TedEd that provides a simple yet detailed explanation of how the immune system works.
Types of vaccines
There are several different types of vaccines that use various mechanisms to 'teach' our immune systems how to fight off specific pathogens. These are:
Inactivated vaccines
Inactivated vaccines use a version of the pathogen that has been killed. These vaccines generally require several doses or boosters for immunity to be ongoing. Examples include Flu, Hepatitis A and Polio.
Live-attenuated vaccines
A live-attenuated vaccine uses a weakened live version of the pathogen, mimicking natural infection without causing serious disease. Examples include Measles, Mumps, Rubella, and Chickenpox.
Messenger RNA (mRNA) vaccines
An mRNA vaccine contains no actual part of the pathogen (alive or dead). This new type of vaccine works by teaching our cells how to make a protein that will in turn, trigger an immune response. In the context of Covid-19 (the only mRNA vaccine approved for use in the form of the Pfizer and Moderna vaccinations), the vaccine instructs our cells in making a protein found on the surface of the Covid-19 virus (the spike protein). This causes our bodies to create antibodies. After delivering the instructions, the mRNA is immediately broken down.4
Subunit, recombinant, polysaccharide, and conjugate vaccines
Subunit, recombinant, polysaccharide, and conjugate vaccines do not contain any whole bacteria or viruses. These vaccines use a piece from the pathogen's surface —like its protein, to elicit a focused immune response. Examples include Hib (Haemophilus influenzae type b), Hepatitis B, HPV (Human papillomavirus), Whooping cough (part of the DTaP combined vaccine), Pneumococcal and Meningococcal disease.5
Toxoid vaccines
Toxoid vaccines are used to protect against pathogens that cause the release of toxins. In these cases, it is the toxins that we need to be protected from. Toxoid vaccines use an inactivated (dead) version of the toxin produced by the pathogen to trigger an immune response. Examples include Tetanus and Diphtheria.6
Viral Vector
A viral vector vaccine uses a modified version of a different virus (the vector) to deliver information in the form of a genetic code from a pathogen to our cells. In the case of the AstraZeneca and Janssen/Johnson & Johnson vaccines and Covid-19, for example, this code teaches the body to make copies of the spike proteins – so if exposure to the actual virus occurs, the body will recognise it and know how to fight it off.7
The video below was developed by Typhoidland and The Vaccine Knowledge Project and describes what happens inside our cells when we are infected with a virus - using Covid-19 as the example.
References
- Science Learning Hub. (2010). The body's first line of defence. Available: https://www.sciencelearn.org.nz/resources/177-the-body-s-first-line-of-defence Last accessed 18 Nov 2021.
- Khan Academy. (Unknown). Innate Immunity. Available: https://www.khanacademy.org/test-prep/mcat/organ-systems/the-immune-system/a/innate-immunity Last accessed 18 Nov 2021.
- Molnar, C., & Gair, J. (2015). Concepts of Biology – 1st Canadian Edition. BCcampus. Retrieved from https://opentextbc.ca/biology/
- Mayo Clinic Staff. (Nov 2021). Different types of COVID-19 vaccines: How they work. Available: https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/different-types-of-covid-19-vaccines/art-20506465 Last accessed 19 Nov 2021.
- Office of Infectious Disease and HIV/AIDS Policy (OIDP). (2021). Vaccine Types. Available: https://www.hhs.gov/immunization/basics/types/index.html Last accessed 16 Nov 2021.
- Vaccine Knowledge Project. (2021). Types of vaccine. Available: https://vk.ovg.ox.ac.uk/vk/types-of-vaccine Last accessed 17 Nov 2021.
- CDC. (Oct 2021). Understanding Viral Vector COVID-19 Vaccines. Available: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/viralvector.html#:~:text=First%2C%20COVID%2D19%20viral%20vector,is%20called%20a%20spike%20protein Last accessed 19 Nov 2021.
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When will there be a vaccine for aspergillosis?
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[et_pb_column type="4_4"][et_pb_text admin_label="Text"]Why are there no vaccines for fungal infections?
Unfortunately, our understanding of immunity to fungi lags far behind our understanding of bacterial or viral infections. There are currently no vaccines available for any fungal infection, but several groups around the world are working towards designing and getting them approved for use in clinics.
The fungal vaccine currently nearest to the finish line is called NDV-3A. It is designed to boost immunity against Candida and prevent vaginal thrush (yeast infection), which will be of great comfort to people suffering from recurrent thrush (4+ infections per year).
Current efforts to produce an Aspergillus vaccine are mainly aimed at preventing invasive aspergillosis, which kills around 200,000 people per year worldwide. Many of these infections could be prevented if we had a way to vaccinate high-risk patients before starting medical treatments that lower their immunity (for example chemotherapy, transplants, strong steroids). However, it is very difficult for a person who already has an existing immunodeficiency to mount an effective immune response.
Efforts are also being made to develop a 'pan-fungal' vaccine, which would protect against many fungal pathogens at once.
What aspergillosis vaccines are in the pipeline?
Several approaches to designing an Aspergillus vaccine have been tried and are starting to achieve promising results in mice. Some researchers have tried injecting purified (recombinant) single proteins, while others have tried using complex mixtures made by fragmenting Aspergillus cell wall matter.
Earlier this year, staff at the Center for Vaccines and Immunology (University of Georgia, USA) tried using a recombinant protein called AF.KEX1, which is naturally found on the surface of Aspergillus cells. Vaccinated mice showed a good antibody response and grew smaller amounts of Aspergillus in their lungs. Importantly, they were less likely to die even if their immune systems were suppressed using corticosteroids.
- Read the research paper: Rayens et al (2021)
- Read an in-depth article about Aspergillus vaccines development: Levitz (2017)
• Read about how the same group used their microbiology skills to help during the COVID-19 pandemic
Will they be used to prevent CPA / ABPA in future?
Even after a vaccine for invasive aspergillosis has been approved, more work will be needed to find out whether it is also effective in preventing CPA and/or ABPA. It is much harder to predict who is at risk of developing chronic forms of aspergillosis because they are so rare even among people who have a known risk factor – most people with COPD do not develop CPA, and most people with asthma do not develop ABPA. This make it very hard to decide who should be vaccinated. It also makes it difficult to recruit enough of the right patients to run a meaningful clinical trial.
So how long?
As with many medical conditions, a prevention is better than a cure. But this is a long-term goal and it is impossible to predict with any accuracy when an Aspergillus vaccine will be available to patients.
We might hope to see some early-stage trials in humans in the next 3-5 years, but there is no guarantee that any of the current candidates will be effective or safe enough in humans to justify larger trials or be rolled out in clinics.
On the other hand, the COVID-19 pandemic has generated an enormous amount of public interest and new technologies for vaccination. Multiple COVID-19 vaccines were developed and brought to the public on a timescale that could scarcely be imagined even just 5 years ago. We may find that the vaccine development landscape changes beyond recognition in the near future and brings the prospect of an Aspergillus vaccine closer than we thought.
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COVID Vaccination Side Effects
[et_pb_section fb_built="1" admin_label="section" _builder_version="4.16" global_colors_info="{}" theme_builder_area="post_content" custom_padding="7px||7px||true|false"][et_pb_row admin_label="row" _builder_version="4.16" background_size="initial" background_position="top_left" background_repeat="repeat" global_colors_info="{}" theme_builder_area="post_content"][et_pb_column type="4_4" _builder_version="4.16" custom_padding="|||" global_colors_info="{}" custom_padding__hover="|||" theme_builder_area="post_content"][et_pb_text admin_label="Text" _builder_version="4.16" background_size="initial" background_position="top_left" background_repeat="repeat" global_colors_info="{}" theme_builder_area="post_content"]Now that the rollout of the second COVID vaccination (using the Pfizer/BioNTech and Oxford/AstraZeneca vaccines) are well underway in the UK attention in our aspergillosis patient communities has turned to the potential for side effects caused by these medications.
Most people suffer few or no side effects from either vaccine other than having a slightly sore arm for a day or two or feeling a few aches. Doctors are recommending that we take paracetamol to relieve those symptoms.
The UK government has now published more detailed information on side effects and all three vaccinations currently in use in the UK (a third vaccine named Moderna has recently started to be used). You can read this information at the links below:
You can also report any suspected side effect.
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