Question about pneumovax immunogenicity

[mhtwus]

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how does pneumovax generate an IgG response if it's against a polysaccharide? i thought polysacchardies and glycoproteins are poorly immunogenic and only produce IgM responses, which is why other vaccines need to be conjugated with toxins?

 

[SeekerOfTheTree]

how does pneumovax generate an IgG response if it's against a polysaccharide? i thought polysacchardies and glycoproteins are poorly immunogenic and only produce IgM responses, which is why other vaccines need to be conjugated with toxins?

They need to be conjugated with proteins and a toxin can serve that role. I believe pneumovax is conjugated to some kind of protein.

 

[cetona]

They need to be conjugated with proteins and a toxin can serve that role. I believe pneumovax is conjugated to some kind of protein.

Pneumovax is not conjugated - it is only the polysaccharide and that is why it isn't given to kids under 2. Prevnar is the conjugated version which is given to kids, but doesn't cover as many different strains. In response to the original question though, I've always wondered that too. You are correct in saying it would only induce IgM, but I don't know why they couldn't just make it as a conjugated vaccine like Prevnar.

 

[SeekerOfTheTree]

Pneumovax is not conjugated - it is only the polysaccharide and that is why it isn't given to kids under 2. Prevnar is the conjugated version which is given to kids, but doesn't cover as many different strains. In response to the original question though, I've always wondered that too. You are correct in saying it would only induce IgM, but I don't know why they couldn't just make it as a conjugated vaccine like Prevnar.

My bad, I got it confused. After 2 the adaptive immune system kicks in. You only conjugate vaccines because children (typically under 2) don't have that response yet and they would only generate IgM. After 2 your body can generate IG against polysacs.

 

[mhtwus]

Pneumovax is not conjugated - it is only the polysaccharide and that is why it isn't given to kids under 2. Prevnar is the conjugated version which is given to kids, but doesn't cover as many different strains. In response to the original question though, I've always wondered that too. You are correct in saying it would only induce IgM, but I don't know why they couldn't just make it as a conjugated vaccine like Prevnar.

yeah according to FA one would expect a purely IgM response, but when i searched google there was some literature describing the mechanism of action that included an IgG response. either the literature is wrong or FA is leaving out some details?

furthermore, what is the nature of vaccine effectiveness with regards to generating IgM-exclusive versus and IgM+IgG response? is it that generating an exclusively-IgM response is not clinically useful? or does a pure-IgM response just make it a not-as-good vaccine? because if the latter were true i could understand the utility of pneumovax, but if the former is true then there must be some way that pneumovax generates IgG immunogenicity... if you get my vibe.

My bad, I got it confused. After 2 the adaptive immune system kicks in. You only conjugate vaccines because children (typically under 2) don't have that response yet and they would only generate IgM. After 2 your body can generate IG against polysacs.

yes. this is true. however i think cetona and i are actually discussing a different issue.

 

[cetona]

My bad, I got it confused. After 2 the adaptive immune system kicks in. You only conjugate vaccines because children (typically under 2) don't have that response yet and they would only generate IgM. After 2 your body can generate IG against polysacs.

I don't know if I agree with that - I don't think the body can ever produce IgG against polysaccharides. Polysaccharides are T-independent, meaning they alone cross-link the surface Ig on B cells. Isotype switching requires interaction with T-cells, which T-independent antigens don't induce, so they always only produce IgM. Polysaccharide vaccines can't be used in kids under two because they can't respond to polysaccharides yet, not because they would only produce IgM.

yeah according to FA one would expect a purely IgM response, but when i searched google there was some literature describing the mechanism of action that included an IgG response. either the literature is wrong or FA is leaving out some details?

furthermore, what is the nature of vaccine effectiveness with regards to generating IgM-exclusive versus and IgM+IgG response? is it that generating an exclusively-IgM response is not clinically useful? or does a pure-IgM response just make it a not-as-good vaccine? because if the latter were true i could understand the utility of pneumovax, but if the former is true then there must be some way that pneumovax generates IgG immunogenicity... if you get my vibe.

I think that the actual immunoglobulins produced from a polysaccharide vaccine are sufficient, but the major issue is that they are T-independent, so there is no memory produced and the effect is not as long-lasting as conjugated vaccines.

 

[SeekerOfTheTree]

I don't know if I agree with that - I don't think the body can ever produce IgG against polysaccharides. Polysaccharides are T-independent, meaning they alone cross-link the surface Ig on B cells. Isotype switching requires interaction with T-cells, which T-independent antigens don't induce, so they always only produce IgM. Polysaccharide vaccines can't be used in kids under two because they can't respond to polysaccharides yet, not because they would only produce IgM.

What other mechanism can you think of for the effectiveness of Pneumovax in people over the age of 2 when it only has polysacchrides in it? There is definately an IgG2 response to the vaccine. I looked up an article to see what type of response the body was generating. A pure IgM response wouldn't be protective against infection.

 

[shouldBstudying]

I think that the actual immunoglobulins produced from a polysaccharide vaccine are sufficient, but the major issue is that they are T-independent, so there is no memory produced and the effect is not as long-lasting as conjugated vaccines.

Which prompts the next natural question... why do we specifically give elderly people only UNconjugated vaccines? Both pneumovax and MPSV-4 are, to my knowledge, both unconjugated vaccines and also the only vaccines approved for each respective bacteria (pneumococcus & meningococcus) for the 55+ bracket in the US. Am I missing something here? Seems counter-intuitive to give those with a declining immune system vaccines that do not promote long-lasting immunity?

 

[mhtwus]

Which prompts the next natural question... why do we specifically give elderly people only UNconjugated vaccines? Both pneumovax and MPSV-4 are, to my knowledge, both unconjugated vaccines and also the only vaccines approved for each respective bacteria (pneumococcus & meningococcus) for the 55+ bracket in the US. Am I missing something here? Seems counter-intuitive to give those with a declining immune system vaccines that do not promote long-lasting immunity?

so let me get this straight, pneumovax generates IgM ONLY, but is still clinically useful, and the question now is why is this the current standard? a legitimate question, but probably not one to be covered on step 1.

 

[SeekerOfTheTree]

so let me get this straight, pneumovax generates IgM ONLY, but is still clinically useful, and the question now is why is this the current standard? a legitimate question, but probably not one to be covered on step 1.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1554633/pdf/clinexpimmunol00039-0056.pdf
I guess IgM predomintes but there is an IG2 and IG1 component as well.

 

[cetona]

What other mechanism can you think of for the effectiveness of Pneumovax in people over the age of 2 when it only has polysacchrides in it? There is definately an IgG2 response to the vaccine. I looked up an article to see what type of response the body was generating. A pure IgM response wouldn't be protective against infection.

Directly from my immunology textbook: "The switch to other isotype, such as IgA and IgG, production requires the presence of cytokines and other signals delivered by locally responding T cells. There is, therefore, little (if any) synthesis of IgG and IgA after exposure to T-independent antigens."

Which prompts the next natural question... why do we specifically give elderly people only UNconjugated vaccines? Both pneumovax and MPSV-4 are, to my knowledge, both unconjugated vaccines and also the only vaccines approved for each respective bacteria (pneumococcus & meningococcus) for the 55+ bracket in the US. Am I missing something here? Seems counter-intuitive to give those with a declining immune system vaccines that do not promote long-lasting immunity?

I've wondered the same thing - I know they cover more strains (23 for pneumovax vs. 13 for prevnar) than the current conjugated vaccines, but I don't know why they give those people unconjugated vaccines. I know that they just recently improved prevnar to 13 strains from 7, so maybe they just haven't been able to produce a conjugated vaccine covering the strains affecting elderly people.

 

[mhtwus]

this may be a stupid question but what is the mechanism for IgM generation against non-peptide antigens in the first place? what cells do the recognition?

 

[cetona]

this may be a stupid question but what is the mechanism for IgM generation against non-peptide antigens in the first place? what cells do the recognition?

The polysaccharides bind directly to membrane immunoglobulins on B cells (monomeric IgM and IgD), which are the antigen receptors on those cells. The extensive size of polysaccharides allows them to cross-link many membrane Ig and activate the B-cell, promoting differentiation into an antibody producing cell.

 

[jpudge12]

Pneumovax has some protein in it...FA 2010 pg 141 in the encapsulated bacteria section

 

[SeekerOfTheTree]

Directly from my immunology textbook: "The switch to other isotype, such as IgA and IgG, production requires the presence of cytokines and other signals delivered by locally responding T cells. There is, therefore, little (if any) synthesis of IgG and IgA after exposure to T-independent antigens."



I've wondered the same thing - I know they cover more strains (23 for pneumovax vs. 13 for prevnar) than the current conjugated vaccines, but I don't know why they give those people unconjugated vaccines. I know that they just recently improved prevnar to 13 strains from 7, so maybe they just haven't been able to produce a conjugated vaccine covering the strains affecting elderly people.

Checkout the article. I understand what the immunology text says but what else explains the IG response that is there? The protective immunity from the vaccine has to have something that is causing more than an IgM response. IgM alone doesn't give you protection, it's like a lambskin condom, won't do much.

 

[mhtwus]

The polysaccharides bind directly to membrane immunoglobulins on B cells (monomeric IgM and IgD), which are the antigen receptors on those cells. The extensive size of polysaccharides allows them to cross-link many membrane Ig and activate the B-cell, promoting differentiation into an antibody producing cell.

thanks!

jpudge12 i think you mean page 139. it seems to be generally the case but microcards and im pretty sure somewhere else in FA says pneumovax is against the polysaccharide capsule. however i admit these are not mutually exclusive since it may be "against the polysaccharide capsule and enhanced with conjugation to a protein"

 

[cetona]

Checkout the article. I understand what the immunology text says but what else explains the IG response that is there? The protective immunity from the vaccine has to have something that is causing more than an IgM response. IgM alone doesn't give you protection, it's like a lambskin condom, won't do much.

I understand what you're saying, and I really don't know - it's probably one of those things where the things we learn in class don't fit neatly into the real world. The article you linked says that the main antibody produced is IgG2, which is still worthless - barely activates complement at all and doesn't act as an opsonin, compared to IgG1 and 3 which do. So I don't really know - for USMLE purposes though, if they ask about a T-independent antigen, say that it only induces IgM.

 

[mhtwus]

I understand what you're saying, and I really don't know - it's probably one of those things where the things we learn in class don't fit neatly into the real world. The article you linked says that the main antibody produced is IgG2, which is still worthless - barely activates complement at all and doesn't act as an opsonin, compared to IgG1 and 3 which do. So I don't really know - for USMLE purposes though, if they ask about a T-independent antigen, say that it only induces IgM.

just to verify my understanding, a T-independent antigen is anything that lacks a peptide component, right?

 

[SeekerOfTheTree]

I understand what you're saying, and I really don't know - it's probably one of those things where the things we learn in class don't fit neatly into the real world. The article you linked says that the main antibody produced is IgG2, which is still worthless - barely activates complement at all and doesn't act as an opsonin, compared to IgG1 and 3 which do. So I don't really know - for USMLE purposes though, if they ask about a T-independent antigen, say that it only induces IgM.

You are right about that.

 

[cetona]

just to verify my understanding, a T-independent antigen is anything that lacks a peptide component, right?

Not necessarily - not all non-peptides can induce a T-independent response (or any response). For example, nucleic acids are non-peptides, but they still don't usually induce an immune response. In general, the important components that induce a T-independent response are polysaccharides and bacterial LPS.

 

[mhtwus]

Not necessarily - not all non-peptides can induce a T-independent response (or any response). For example, nucleic acids are non-peptides, but they still don't usually induce an immune response. In general, the important components that induce a T-independent response are polysaccharides and bacterial LPS.

thanks cetona, you've been really helpful. however in what is now becoming a recurring theme, this has spawned some more questions...

Is the B-cell IgM response induced by both polysaccharides and LPS?

Secondly, am i correct in saying the complement lectin-pathway only activated by LPS (and not polysaccharide)?

thanks all!

 

[cetona]

thanks cetona, you've been really helpful. however in what is now becoming a recurring theme, this has spawned some more questions...

Is the B-cell IgM response induced by both polysaccharides and LPS?

Secondly, am i correct in saying the complement lectin-pathway only activated by LPS (and not polysaccharide)?

thanks all!

I believe both of those things are true.

 

[shouldBstudying]

a legitimate question, but probably not one to be covered on step 1.

I feel like this quote basically is, in a nutshell, my step 1 studying.

 

[mhtwus]

I feel like this quote basically is, in a nutshell, my step 1 studying.

well yeah the content that can be covered in 322 questions means they can't even cover half of first aid, much less the entire field...

so chances are, that point you're studying right now won't show up on the real thing.