encapsulated bacterial vaccines??

[Aclamity]

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I always thought that the encapsulated bacteria (S. pneumo, H. influenze, N. meningitidis) were vaccinated with with capsule Ag conjugated to protein (e.g. diphtheria toxoid). This is confirmed on pg. 149 in FA.

However I've gotten 2 questions in the last few days (1 in UW and 1 in Kaplan) that imply the vaccines are ONLY capsular polysaccharide antigen. And getting the question right hinges on you knowing that fact. What's the deal?

 

[mdeast]

I always thought that the encapsulated bacteria (S. pneumo, H. influenze, N. meningitidis) were vaccinated with with capsule Ag conjugated to protein (e.g. diphtheria toxoid). This is confirmed on pg. 149 in FA.

However I've gotten 2 questions in the last few days (1 in UW and 1 in Kaplan) that imply the vaccines are ONLY capsular polysaccharide antigen. And getting the question right hinges on you knowing that fact. What's the deal?

Hmmm that's weird? Can you paste the questions?

Diptheria toxoid is basically an adjuvant to other vaccines like the capsular polsysaccharide vaccines for H. Flu, etc. I'm not sure if you necessarily *need* the toxoid to confer immunity to the respective bug, just that you need to know the toxoid addition helps boost the immune response. Seems silly they would ask a question trying to differentiate whether it is actually added or not.

 

[ipizzy]

Pneumococcus: there is a vaccine (23-valent pneumovax) that is *only* polysaccharide; no protein conjugate. Pneumovax is used in adults (especially those at risk for pneumococcal infection, like asthmatics or immunocompromised). Kids do not mount sufficient immunity to pneumovax since their immune systems are not good enough at T-cell independent immunity.

The conjugate 13-valent pneumococcal vaccine (Prevnar-13) was only recently approved for use in people age 50 and older. This is the one you use in kiddos under age 5.

Meningococcus: There are 3 vaccines available for meningococcus in the US. Two of them are protein conjugates (Menactra and Menveo), and one of them is polysaccharide-only (Menomune). All of these vaccines are quadrivalent and protect against 4 of the 6 most common subtypes of meningococcus that are responsible for meningococcal meningitis. Menomune is used only in adults aged 55 and up. The protein conjugates are the ones used in kids or young adults.

H. flu: again, you always give kids the protein conjugate vaccine against Hib (3 different conjugate vaccines, each using a different protein conjugate, are available: mutant diphtheria protein, meningococcal group B outer membrane protein, or tetanus toxoid). There is also a polysaccharide-only version of the Hib vaccine, but it was withdrawn from the market in 1988 since it doesn't work well at all in kids (who are the major at-risk group for Hib infection).

TL;DR: there are polysaccharide-only versions of vaccines against H. flu/meningococcus/pneumococus. Choice of polysaccharide-only vs. protein-conjugate depends on the age of the patient and oftentimes their immune status.

 

[Aclamity]

Hmmm that's weird? Can you paste the questions?

Diptheria toxoid is basically an adjuvant to other vaccines like the capsular polsysaccharide vaccines for H. Flu, etc. I'm not sure if you necessarily *need* the toxoid to confer immunity to the respective bug, just that you need to know the toxoid addition helps boost the immune response. Seems silly they would ask a question trying to differentiate whether it is actually added or not.

Sure. I don't remember the exact question, but it went basically like this:

1. college student presents with signs/symptoms of meningitis. You give him a vaccine containing:
a) Capsular polysaccharide
b) inactivated toxoid
c-e) other stuff that was wrong

(a) was the answer, which makes sense, but I don't really get why (b) is wrong

2. Middle-aged woman gets splenectomy. You give her a vaccine that induces:
a) IgM response ONLY
b) IgG response
c-e) other stuff

Again, (a) was the right answer, but IgGs would be produced with a conjugate vaccine, so I thought (b) should be correct


I thought maybe my understanding of the questions/vaccines was flawed, but then both answer explanations clearly said that you give "a vaccine with capsular Ag, which doesn't allow patient to isotype-switch."

 

[ijn]

The toxoid is providing immunity to diptheria toxoid. It's not conferring resistance to Neisseria, Haemophillus, or Strep. It increases the immunogenicity of polysaccharide vaccines but it provides actual immunity to an entirely separate organism.

Polysaccharides only produce IgM responses. You get IgG to the toxoid, but that isn't providing you any IgG immunity to Neisseria, Haemophilus, or Strep. So If I gave a 2 year old the HiB vaccine (capsular polysaccharide of H. flu + diptheria toxoid) they'd generate IgM response to H. flu and an early IgM/late IgG reponse to diptheria toxoid. No IgG to H. flu will be generated.

For the college age kid and the spleenless woman, you're trying to induce immunity to capsular polysaccharides. They may be conjugated to some protein, but the point of the vaccine is not the conjugated protein. The woman without a spleen is susceptible to S. pneumonia, not tetanus. The kid at college is susceptible to N. meningitis, not diptheria.

 

[MrBeauregard]

The toxoid is providing immunity to diptheria toxoid. It's not conferring resistance to Neisseria, Haemophillus, or Strep. It increases the immunogenicity of polysaccharide vaccines but it provides actual immunity to an entirely separate organism.

Polysaccharides only produce IgM responses. You get IgG to the toxoid, but that isn't providing you any IgG immunity to Neisseria, Haemophilus, or Strep. So If I gave a 2 year old the HiB vaccine (capsular polysaccharide of H. flu + diptheria toxoid) they'd generate IgM response to H. flu and an early IgM/late IgG reponse to diptheria toxoid. No IgG to H. flu will be generated.

For the college age kid and the spleenless woman, you're trying to induce immunity to capsular polysaccharides. They may be conjugated to some protein, but the point of the vaccine is not the conjugated protein. The woman without a spleen is susceptible to S. pneumonia, not tetanus. The kid at college is susceptible to N. meningitis, not diptheria.

I don't think this is correct.

 

[Aclamity]

The toxoid is providing immunity to diptheria toxoid. It's not conferring resistance to Neisseria, Haemophillus, or Strep. It increases the immunogenicity of polysaccharide vaccines but it provides actual immunity to an entirely separate organism.

Polysaccharides only produce IgM responses. You get IgG to the toxoid, but that isn't providing you any IgG immunity to Neisseria, Haemophilus, or Strep. So If I gave a 2 year old the HiB vaccine (capsular polysaccharide of H. flu + diptheria toxoid) they'd generate IgM response to H. flu and an early IgM/late IgG reponse to diptheria toxoid. No IgG to H. flu will be generated.

For the college age kid and the spleenless woman, you're trying to induce immunity to capsular polysaccharides. They may be conjugated to some protein, but the point of the vaccine is not the conjugated protein. The woman without a spleen is susceptible to S. pneumonia, not tetanus. The kid at college is susceptible to N. meningitis, not diptheria.

Hold on, the way we learned it in class was that if the vaccine was ONLY a capsular polysaccharide it would only elicit an IgM response from B-cells because the B-cells will take up the polysaccharide, but won't be able to present it on MHC II molecules (which only present peptides). So it will be stuck making IgM pentamers against the capsule.

If you conjugate a protein toxoid to the capsule, now the B-cell can bind to the capsule, take it up, break it apart, and present the toxoid epitope on its MHC II. This can now interact with Th1 cells, Th1 cells will release IL4 & 5, and will allow the B-cell to produce IgG. Even though the T-cell is interacting with the toxoid epitope the immunoglobulins that are created are dependent on the epitope that the B-cell's membrane-bound IgM originally bound to (which was the capsule polysaccharide).

Correct me if I'm wrong, but this should lead to IgG production against the capsule

 

[MrBeauregard]

Vaccines that utilize capsular polysaccharide can only induce the production of IgM. This is because polysaccharide cannot be presented in the groove of MHC-II and, as a result, can only induce a T-independent immune response: only IgM is produced and no memory B-cells are created.

Vaccines that conjugate capsular polysaccharide with a protein fragment can induce a T-dependent immune response. This is because the protein fragment, which is covalently linked to the polysaccharide, can be displayed in the groove of MHC-II. This allows T-helper cells to be activated, which can then produce IL-4 (and IL-5 and IL-10) which then aids in isotype switching and the production of IgG.

This is the entire reason conjugate vaccines were created.

To answer OP's original question: I have seen both of those questions in reference to S. pneumo in Kaplan Qbank and UWorld. The key to the answer was knowing that the adult S. pneumo vaccine is a polysaccharide vaccine, not a conjugate. As a result, only IgM is produced in these individuals. I haven't seen the question about Neisseria.

 

[ijn]

Gotcha, so Pneumovax is IgM, and meningococcal and H. flu are IgG?

 

[The kitchen sink]

This is a bit topic, but from various others sources I have that in addition to the FA stated Strep Pneumo, H. Influ, Neisseria, Salmonella, Klebsiella and Group B strep that Crytococcus Neoformans and Psuedomonas are also encapsulated organisms. Is this true?

 

[MrBeauregard]

This is a bit topic, but from various others sources I have that in addition to the FA stated Strep Pneumo, H. Influ, Neisseria, Salmonella, Klebsiella and Group B strep that Crytococcus Neoformans and Psuedomonas are also encapsulated organisms. Is this true?

Yes, it is true that C. neoformans is encapsulated, and it is apparently an extremely high-yield fact to know, as I have encountered probably ~15 UWorld questions that reference that fact. It mainly causes meningitis in those who are immunocompetent but also causes pulmonary disease in immunocompromised hosts. It stains red with mucicarmine in bronchoalveolar lavage fluid. It will have a large, clear rim when stained with India ink. The absolute best way to diagnose a cryptococcal infection is with a latex agglutination test, which utilizes the presence of the aforementioned capsule.

And yes, P. aeruginosa is an encapsulated organism. It also has a slime layer which allows it to cause catheter-associated UTIs as well as ventilator-associated pneumonia. This is also off-topic, but I just found out that Pseudomonas cepacia (also known as Burkholderia cepacia) is a catalase-positive organism that causes serious infections in patients with CGD.

 

[Aclamity]

This is also off-topic, but I just found out that Pseudomonas cepacia (also known as Burkholderia cepacia) is a catalase-positive organism that causes serious infections in patients with CGD.

To add to this, I started keeping a list of the catalase (+) organisms mentioned in FA and as I'm going through UW. I noticed that all the lists in FA were inconsistent/incomplete. But what I've gathered from everything, here they are:

S. aureus, Pseudomonas, Aspergillus, Candida, E. coli, S. typhi, Klebsiella, Nocardia, Serratia.

Can anyone confirm if those are true?

 

[MrBeauregard]

To add to this, I started keeping a list of the catalase (+) organisms mentioned in FA and as I'm going through UW. I noticed that all the lists in FA were inconsistent/incomplete. But what I've gathered from everything, here they are:

S. aureus, Pseudomonas, Aspergillus, Candida, E. coli, S. typhi, Klebsiella, Nocardia, Serratia.

Can anyone confirm if those are true?

I'll type up my list here in a little while. One thing I have gathered is that not all catalase (+) organisms actually cause infections in patients with CGD. I'm sure it would be good to know the list of all which are positive, but UWorld made a point to say that even though there are other catalase (+) organisms, only certain ones cause disease for some reason or another.