Questions concerning "vaccines" in general

[Mikko]

Hi, can anyone help me to answer my two questions concerning vaccines? I can´t find any useful scientific review or article where I can find the answer:

1. If you were a scientist and you had to find a vaccine against a particular pathogen: which way of delivery would you choose? I.v., i.m., subcutaneouly, or oral application... does anyone have an overview? And the precise mechanisms behind each particular application??

2. It seems to be sometimes absolutely essential to use an adjuvant (like alum) to "stimulate" the innate immune system (the toll-like-receptor pathway for example) - BUT: there are also vaccines without any adjuvants; they seem to stimulate the innate IS on their own. WHY?

 

I would be so grateful if someone could help me! Thanks.

[insane_alien]

1/ the delivery method would depend on the what you actually produce rather than a choice made before research has begun. a lot of vaccines would be destroyed in the stomach if taken orally.

 

2/ i have no idea on this one but it seems likely(to me) that a vaccine consisting of a weakened microbe wouldn't require prompting while a vaccine composed of a dead microbe would. hopefully someone with more knowledge than me will clarify.

[Mikko]

thanks for your answers!

 

1) sorry, my formulation (or rather the example) was not good enough. what I wanted to say is: of course, you already know the pathogen and the natural way this pathogen enters the host. What I know is that vaccine research has always the goal to find a delivery method that is easy and cheap (pills are easier to applicate to thousands of people than injections for instance). but what if you neglect this fact. what is "the best way" to stimulate the immune system and what are the mechanisms?

 

2) well, I ve thought of this, but unfortunately its not that easy... an example: I´ve read that there was a dead vaccine (I don´t remember the name, but it was against influenza) which was first produced with an adjuvants and then they ve seen that it also works without adjuvants - does this make sense? It seems like it is not really known in which case one need an adjuvants and in which case not.

[GDG]

Hi, can anyone help me to answer my two questions concerning vaccines? I can´t find any useful scientific review or article where I can find the answer:

1. If you were a scientist and you had to find a vaccine against a particular pathogen: which way of delivery would you choose? I.v., i.m., subcutaneouly, or oral application... does anyone have an overview? And the precise mechanisms behind each particular application??

2. It seems to be sometimes absolutely essential to use an adjuvant (like alum) to "stimulate" the innate immune system (the toll-like-receptor pathway for example) - BUT: there are also vaccines without any adjuvants; they seem to stimulate the innate IS on their own. WHY?

 

I would be so grateful if someone could help me! Thanks.

 

Vaccines are still not understood in complete detail, so in general you still need to experiment.

 

With regard to mode of delivery, to some extent this can depend on what form of response you want. Administering a live oral attenuated virus to the GI tract seems to be good for stimulating mucosal immunity (IgA antibodies), while intramuscual injection is generally good for IgG.

 

Adjuvants basically boost the immune response. Your immune response inherently recognizes some antigens as pathogenic, and responds automatically. Muramyl-peptide adjuvants seem to trigger a specific receptor that stimulates rapid response (muramyl-peptides are found mainly in mycobacteria capsules, e.g., M. tuberculosis). Adjuvants like alum still have not been fully explained (see, e.g., E. DiGregorio et al., Curr Opin Immunol (2009) 21:339-45). Vaccines that work without adjuvants probably contain antigens that are sufficiently recognized by the innate system.

[Mikko]

While looking for further information I´ve found this paper:

Storni Tazio et al., Immunity in response to particulate antigen-delivery systems. Advanced drug delivery reviews 2005;57(3):333-55.

It´s the best I´ve found...

 

Well, unfortunately I have another question (of course it would be nice if you could help me to find the answer):

What about boosting: why do some pathogens (like the virus causing measles) induce lifelong immunity while others need one or more so-called "booster immunizations"? What does "fading memory" stands for? Is anything known so far about the mechanisms?

[Mr Skeptic]

1. If you were a scientist and you had to find a vaccine against a particular pathogen: which way of delivery would you choose? I.v., i.m., subcutaneouly, or oral application...

 

I guess oral is the favorite, but it will also destroy many types of vaccines or even medicines, and has inefficient absorption. Basically, it depends on what substance you are talking about.

 

2. It seems to be sometimes absolutely essential to use an adjuvant (like alum) to "stimulate" the innate immune system (the toll-like-receptor pathway for example) - BUT: there are also vaccines without any adjuvants; they seem to stimulate the innate IS on their own. WHY?

 

In some cases, the adjuvant can be replaced by larger quantities of vaccine. However, that can be more expensive (if the additional vaccine costs more than the adjuvant) and perhaps more dangerous (for a weakened rather than dead vaccine). From what I hear, lots of new vaccines are trying to train the immune system to attack a small hidden target, because the big obvious target tends to be the part of the organism that is there to protect it against the immune system and can easily change so the immune system can't recognize it.