Vaccine against MAC?

Posted by Armando @bolso1, Nov 19, 2020

Does anybody know about a vaccine against MAC? I found the paper ["Protection against Mycobacterium avium by DNA Vaccines Expressing Mycobacterial Antigens as Fusion Proteins with Green Fluorescent Protein" (INFECTION AND IMMUNITY, Aug. 1999, Vol. 67, No. 8 p. 4243–4250)] that claimed to be "...first report of successful DNA vaccination against M. avium", but nothing else.

Interested in more discussions like this? Go to the MAC & Bronchiectasis Support Group.

@rits

A promising event recently occurred that some day may bring help to us. On November 13, Insmed, the pharmaceutical company behind Arikayce, received a PRIME designation from the European Medicine Agency for their drug BRENSOCATIB. This drug is an oral med that stops the release of a protein that actuates neutrophils which release an enzyme that damages the lungs of people with bronchiectasis.

A PRIME designation supports continuing research to bring promising treatment to patients.

Jump to this post

@rits that is great news, thanks to Insmed.

REPLY
@sueinmn

Sorry, but the harsh reality is that health research and care funds are limited and developing a vaccine is extremely expensive, and in many cases "iffy" proposition. Dollars are allocated where drug companies and/or the government will get the most return on investment. Both my husband and niece have been involved in health care research, through a university that gets grants from the government and drug companies. Promising projects are abandoned all the time because the money isn't available and/or the perceived demand is inadequate.

As for global reach, I think you are still talking about a relatively small percentage of the population, and the number of places that even recognize and treat MAI are not huge. The sad fact is that a lot of the world population is still worried about keeping babies alive to grow into adulthood, providing adequate food and safe water and vaccinating for contagious diseases. Problems like MAI are not even on their radar.

I'm not trying to be argumentative, just pointing out that in the face of scarce resources, things that are worthwhile to small parts of the population fall by the wayside. This is even true of subsets of "headline" diseases like cancer - the rare ones don't get the same research as common ones.

Sue

Jump to this post

Hello Sue. I know that folks with bronchiectasis count as a small number, but I wonder if adding patients with CF and other lung diseases that also are prone to mac would be enough to push us out of the 'orphan disease' catagory?

REPLY
@windwalker

Hello Sue. I know that folks with bronchiectasis count as a small number, but I wonder if adding patients with CF and other lung diseases that also are prone to mac would be enough to push us out of the 'orphan disease' catagory?

Jump to this post

Hi Terri - That's an interesting question.
First, I looked up "orphan diseases" - in the US it is defined as less than 200,000 people affected.
Then I looked up the number of people in the US with bronchiectasis - the estimate is from 350,000 - 500,000 people - so not an orphan.
Then I looked up the number of CF patients in the US - 30,000 total - probably because the average life span for CF is still under 50 yrs.
Other people prone to NTM include ventilator-dependent, HIV positive and COPD patients among others.
And for NTM (all non-tubercular mycobacteria) infections in the US - 86,000 currently - includes all forms and all underlying conditions.
Finally, for comparison, I looked up the number of people in the US with TB - current estimate is 13 million, and the number of shingles cases per year is about 1.4 million.

So there are enough people at risk for NTM to make it "not an orphan" but since the actual number of cases is low, and it is not easily transmissible between people, I suspect only a concerted campaign and the ability to raise funds would be the only way toget vaccine research kick-started.

If anyone has the passion, time and energy for such an undertaking, that would be great.

Sue

REPLY
@sueinmn

Hi Terri - That's an interesting question.
First, I looked up "orphan diseases" - in the US it is defined as less than 200,000 people affected.
Then I looked up the number of people in the US with bronchiectasis - the estimate is from 350,000 - 500,000 people - so not an orphan.
Then I looked up the number of CF patients in the US - 30,000 total - probably because the average life span for CF is still under 50 yrs.
Other people prone to NTM include ventilator-dependent, HIV positive and COPD patients among others.
And for NTM (all non-tubercular mycobacteria) infections in the US - 86,000 currently - includes all forms and all underlying conditions.
Finally, for comparison, I looked up the number of people in the US with TB - current estimate is 13 million, and the number of shingles cases per year is about 1.4 million.

So there are enough people at risk for NTM to make it "not an orphan" but since the actual number of cases is low, and it is not easily transmissible between people, I suspect only a concerted campaign and the ability to raise funds would be the only way toget vaccine research kick-started.

If anyone has the passion, time and energy for such an undertaking, that would be great.

Sue

Jump to this post

In the meantime, I am interested in exploring more the possibilities of the already available BCG vaccine, based on the results that I shared a week ago.

REPLY
@sueinmn

Hi Terri - That's an interesting question.
First, I looked up "orphan diseases" - in the US it is defined as less than 200,000 people affected.
Then I looked up the number of people in the US with bronchiectasis - the estimate is from 350,000 - 500,000 people - so not an orphan.
Then I looked up the number of CF patients in the US - 30,000 total - probably because the average life span for CF is still under 50 yrs.
Other people prone to NTM include ventilator-dependent, HIV positive and COPD patients among others.
And for NTM (all non-tubercular mycobacteria) infections in the US - 86,000 currently - includes all forms and all underlying conditions.
Finally, for comparison, I looked up the number of people in the US with TB - current estimate is 13 million, and the number of shingles cases per year is about 1.4 million.

So there are enough people at risk for NTM to make it "not an orphan" but since the actual number of cases is low, and it is not easily transmissible between people, I suspect only a concerted campaign and the ability to raise funds would be the only way toget vaccine research kick-started.

If anyone has the passion, time and energy for such an undertaking, that would be great.

Sue

Jump to this post

@sueinmn Well, that is very interesting information Sue. Thank you for finding/sharing that. irene5

REPLY
@bolso1

In the meantime, I am interested in exploring more the possibilities of the already available BCG vaccine, based on the results that I shared a week ago.

Jump to this post

After rereading the article you posted, I suggest you contact the authors to learn the current status of their research.
Sue

REPLY
@bolso1

Here are a few references on the ecology of NTM that, while they do not address specifically the increase in rates of pulmonary NTM, provide information about conditions that favor such increases.
1. Health impacts of environmental mycobacteria. Todd P Primm, Christie A Lucero, Joseph O Falkinham 3rd. Clin Microbiol Rev. 2004 Jan;17(1):98-106. doi: 10.1128/cmr.17.1.98-106.2004. Abstract: Environmental mycobacteria are emerging pathogens causing opportunistic infections in humans and animals. The health impacts of human-mycobacterial interactions are complex and likely much broader than currently recognized. Environmental mycobacteria preferentially survive chlorination in municipal water, using it as a vector to infect humans. Widespread chlorination of water has likely selected more resistant environmental mycobacteria species and potentially explains the shift from M. scrofulaceum to M. avium as a cause of cervical lymphadenitis in children. Thus, human activities have affected mycobacterial ecology. While the slow growth and hydrophobicity of environmental mycobacteria appear to be disadvantages, the unique cell wall architecture also grants high biocide and antibiotic resistance, while hydrophobicity facilitates nutrient acquisition, biofilm formation, and spread by aerosolization. The remarkable stress tolerance of environmental mycobacteria is the major reason they are human pathogens. Environmental mycobacteria invade protozoans, exhibiting parasitic and symbiotic relationships. The molecular mechanisms of mycobacterial intracellular pathogenesis in animals likely evolved from similar mechanisms facilitating survival in protozoans. In addition to outright infection, environmental mycobacteria may also play a role in chronic bowl diseases, allergies, immunity to other pulmonary infections, and the efficacy of bacillus Calmette-Guerin vaccination.
2. Ecology of nontuberculous mycobacteria--where do human infections come from?Joseph O Falkinham 3rd. Semin Respir Crit Care Med. 2013 Feb;34(1):95-102. doi: 10.1055/s-0033-1333568. Epub 2013 Mar 4. Abstract: Nontuberculous mycobacteria (NTM) are environmental, opportunistic human pathogens whose reservoirs include peat-rich potting soil and drinking water in buildings and households. In fact, humans are likely surrounded by NTM. NTM are ideally adapted for residence in drinking water distribution systems and household and building plumbing as they are disinfectant-resistant, surface adherent, and able to grow on low concentrations of organic matter. For individuals at risk for NTM infection, measures can be taken to reduce NTM exposure. These include avoiding inhalation of dusts from peat-rich potting soil and aerosols from showers, hot tubs, and humidifiers. A risk analysis of the presence of NTM in drinking water has not been initiated because the virulence of independent isolates of even single NTM species (e.g., Mycobacterium avium) is quite broad, and virulence determinants have not been identified.
3. Environmental sources of nontuberculous mycobacteria. Joseph O Falkinham 3rd. Clin Chest Med. 2015 Mar;36(1):35-41. doi: 10.1016/j.ccm.2014.10.003. Abstract: Nontuberculous mycobacteria (NTM) include over 150 species. The source for human infection is the environment. NTM are normal inhabitants of soil and drinking water. NTM grow and persist in many buildings. They are not contaminants of drinking water, but members of the natural drinking water microbial population. Infection occurs because humans share the same habitats. Because the ecology, antibiotic susceptibility, and virulence of individual species differs, identifying NTM isolates to species is important. Treatment requires multiple antibiotics. NTM patients are innately sensitive to NTM infection, resulting in reinfection. Knowledge of the sources of NTM can reduce exposure to environmental NTM.
4. Current Epidemiologic Trends of the Nontuberculous Mycobacteria (NTM). Joseph O Falkinham 3rd. Curr Environ Health Rep. 2016 Jun;3(2):161-7. doi: 10.1007/s40572-016-0086-z. Abstract: The nontuberculous mycobacteria (NTM) are waterborne opportunistic pathogens of humans. They are normal inhabitants of premise plumbing, found, for example, in household and hospital shower heads, water taps, aerators, and hot tubs. The hydrophobic NTM are readily aerosolized, and pulmonary infections and hypersensitivity pneumonitis have been traced to the presence of NTM in shower heads. Hypersensitivity pneumonitis in automotive workers was traced to the presence of NTM in metal recovery fluid used in grinding operations. Recently, NTM bacteremia in heart transplant patients has been traced to the presence of NTM in water reservoirs of instruments employed in operating rooms to heat and cool patient blood during periods of mechanical circulation. Although NTM are difficult to eradicate from premise plumbing as a consequence of their disinfectant-resistance and formation of biofilms, measures such as reduction of turbidity and reduction in carbon and nitrogen for growth and the installation of microbiological filters can reduce exposure of NTM to susceptible individuals.

Jump to this post

@bolso1 I was vaccinated against TB in 1974 or ’75 because I went to Nepal in the Peace Corps. The vaccination is not recorded in my little yellow international vaccination book, but I distinctly remember the process and being told that I might test positive for TB because of the vaccine. I have no scar, but I also have no scars from my smallpox vaccinations. In 2018, at age 70, I was diagnosed with focal bronchiectasis, nodules, and MAC after I coughed up blood while lap swimming. I have not been tested for MAC since. My only symptoms are coughing up minor sputum in the morning and occasional minor coughing during the day. (I've also had acid reflux for many years.)

I walk 2-3 miles nearly every day, and do other exercises. I stopped the lap swimming because that’s probably where I caught MAC. Until this year, we lived Michigan in summer and near Tucson in winter. This summer we sold our AZ home and are trying all year in Michigan. I love to “work” frequently on our 2 acres of woods and wetland, which I have been doing for 10 years while not wearing a mask. My only “treatment” is once/day nebulizing with 7% saline, which I started this past March because of this forum.

According to the nhs.uk: “The BCG vaccination is thought to protect up to 80% of people against the most severe forms of TB for at least 15 years, perhaps even up to 60 years.” Perhaps the old vaccine is the reason my MAC is not severe (??).

REPLY
@lorifilipek

@bolso1 I was vaccinated against TB in 1974 or ’75 because I went to Nepal in the Peace Corps. The vaccination is not recorded in my little yellow international vaccination book, but I distinctly remember the process and being told that I might test positive for TB because of the vaccine. I have no scar, but I also have no scars from my smallpox vaccinations. In 2018, at age 70, I was diagnosed with focal bronchiectasis, nodules, and MAC after I coughed up blood while lap swimming. I have not been tested for MAC since. My only symptoms are coughing up minor sputum in the morning and occasional minor coughing during the day. (I've also had acid reflux for many years.)

I walk 2-3 miles nearly every day, and do other exercises. I stopped the lap swimming because that’s probably where I caught MAC. Until this year, we lived Michigan in summer and near Tucson in winter. This summer we sold our AZ home and are trying all year in Michigan. I love to “work” frequently on our 2 acres of woods and wetland, which I have been doing for 10 years while not wearing a mask. My only “treatment” is once/day nebulizing with 7% saline, which I started this past March because of this forum.

According to the nhs.uk: “The BCG vaccination is thought to protect up to 80% of people against the most severe forms of TB for at least 15 years, perhaps even up to 60 years.” Perhaps the old vaccine is the reason my MAC is not severe (??).

Jump to this post

I don't know whether the vaccine helps to explain the lesser severity of MAC in your case. However, I have kept investigating and found a couple of interesting references (pdfs attached). One reports the findings in Finland where universal BCG vaccination was stopped in 2006 (Kontturi A, Soini H, Ollgren J, Salo E. Increase in Childhood Nontuberculous Mycobacterial Infections After Bacille Calmette-Guerin Coverage Drop: A Nationwide, Population-Based Retrospective Study, Finland, 1995-2016. Clin Infect Dis. 2018;67(8):1256–61), and the conclusions were "After infant BCG coverage in Finland decreased, childhood NTM infections increased drastically. As there is no other apparent cause for the increase, this indicates that BCG offers protection against childhood NTM disease. This observation adds to the understanding of childhood NTM epidemiology and might explain why the disease is emerging in some countries." The other paper is about a similar study in the Czech Republic (Trnka L, Dankova D, Svandova E. Six years’ experience with the discontinuation of BCG vaccination. 4. Protective effect of BCG vaccination against the Mycobacterium avium intracellulare complex. Tuber Lung Dis. 1994;75(5):348–52), in which the authors concluded "In non-BCG vaccinated children the incidence of lymphadenitis caused by M. avium complex was considerably higher than in vaccinated children. BCG cells possess antigenic determinants which confer protective immunity probably both against M. tuberculosis and against M. avium complex infections. It may thus be assumed that BCG vaccination protects both against pathogenic tubercle bacilli and M. avium complex. This should be taken into consideration before recommending discontinuation of mass BCG vaccination of newborns in areas with a high prevalence of M. avium complex infection."

Shared files

Infections After Bacille Calmette-Guérin Coverage Drop A Nationwide, Population-Based Retrospective Study, Finland, 1995-2016 (Infections-After-Bacille-Calmette-Guerin-Coverage-Drop-A-Nationwide-Population-Based-Retrospective-Study-Finland-1995–2016.pdf)

Six years' experience with the discontinuation of BCG vaccination (Six-years-experience-with-the-discontinuation-of-BCG-vaccination.pdf)

REPLY
@bolso1

I don't know whether the vaccine helps to explain the lesser severity of MAC in your case. However, I have kept investigating and found a couple of interesting references (pdfs attached). One reports the findings in Finland where universal BCG vaccination was stopped in 2006 (Kontturi A, Soini H, Ollgren J, Salo E. Increase in Childhood Nontuberculous Mycobacterial Infections After Bacille Calmette-Guerin Coverage Drop: A Nationwide, Population-Based Retrospective Study, Finland, 1995-2016. Clin Infect Dis. 2018;67(8):1256–61), and the conclusions were "After infant BCG coverage in Finland decreased, childhood NTM infections increased drastically. As there is no other apparent cause for the increase, this indicates that BCG offers protection against childhood NTM disease. This observation adds to the understanding of childhood NTM epidemiology and might explain why the disease is emerging in some countries." The other paper is about a similar study in the Czech Republic (Trnka L, Dankova D, Svandova E. Six years’ experience with the discontinuation of BCG vaccination. 4. Protective effect of BCG vaccination against the Mycobacterium avium intracellulare complex. Tuber Lung Dis. 1994;75(5):348–52), in which the authors concluded "In non-BCG vaccinated children the incidence of lymphadenitis caused by M. avium complex was considerably higher than in vaccinated children. BCG cells possess antigenic determinants which confer protective immunity probably both against M. tuberculosis and against M. avium complex infections. It may thus be assumed that BCG vaccination protects both against pathogenic tubercle bacilli and M. avium complex. This should be taken into consideration before recommending discontinuation of mass BCG vaccination of newborns in areas with a high prevalence of M. avium complex infection."

Jump to this post

@bolso1 Unfortunately, the BCG vaccine is much less effective on older adults: "There's no evidence the BCG vaccine works for people over the age of 35." https://www.nhs.uk/conditions/vaccinations/when-is-bcg-tb-vaccine-needed/ and https://www.cdc.gov/tb/publications/factsheets/prevention/bcg.htm

Btw, if you'll notice from Terri's (@windwalker) comments above on various likely places one is exposed to MAC, the members of this forum have been doing lots of research on various aspects of MAC and bronchiectasis over the years. Terri alerted us (and many doctors) to the efficacy of nebulizing with 7% saline to help kill off MAC. @windwalker can give you links to the articles she's given us on that topic.

REPLY
@lorifilipek

@bolso1 Unfortunately, the BCG vaccine is much less effective on older adults: "There's no evidence the BCG vaccine works for people over the age of 35." https://www.nhs.uk/conditions/vaccinations/when-is-bcg-tb-vaccine-needed/ and https://www.cdc.gov/tb/publications/factsheets/prevention/bcg.htm

Btw, if you'll notice from Terri's (@windwalker) comments above on various likely places one is exposed to MAC, the members of this forum have been doing lots of research on various aspects of MAC and bronchiectasis over the years. Terri alerted us (and many doctors) to the efficacy of nebulizing with 7% saline to help kill off MAC. @windwalker can give you links to the articles she's given us on that topic.

Jump to this post

Yes, the BCG vaccine has variable efficacy on TB, but we need to know more about its efficacy on NTM. Thank you!

REPLY
Please sign in or register to post a reply.