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Honours Track: Vaccination and transplantation

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In the previous lecture you have already heard of the his risk of infection and cancer caused by the immunosuppression to prevent allograft rejection another downside of this immunosuppression is that the immune response to vaccines is suppressed as well vaccination may be ineffective or even unsafe in this lecture we will focus on vaccination after transplantation

After viewing this lecture you’ll be able to understand how immunosuppressive medication affects the immune response to vaccines you will know under which conditions vaccination is safe and effective and which vaccines may be useful before and after transplantation let’s take a look at this case study a 37 year old physiotherapist wants to travel to nepal for four weeks

She has received a renal transplant more than ten years ago the renal function is well preserved on the prednisone and mofa till mycophenolate now what would happen if he would vaccinate her with hepatitis a vaccine is it safe and would it help well there are two kinds of vaccines inactivated vaccines and live attenuated vaccines hepatitis a vaccine is an inactivated

Virus vaccine this means that a hepatitis a vaccine virus does not replicate after injection all inactivated vaccines are therefore safe in contrast measles mumps rubella vaccine varicella zoster vaccine yellow fever vaccine and bcg are live attenuated vaccines these vaccines will replicate after injection the subsequent infection can become life-threatening in case

Were failing immune response live attenuated vaccines are unsafe in severely animus oppressed individuals and should not be given to transplant recipients now back to our patient what happens after injection of hepatitis a vaccine the immune response to an inactivated vaccine like hepatitis a vaccine is mounted in the draining lyme lymph node of the injection site

Antigen presenting cells taken up the vaccine antigens at the site of injection presents small fragments of these antigens to passing t and b cells in the lymph node upon recognition and after receiving appropriate co-stimulatory signals these lymphocytes will be activated as has been discussed before activation of t-cells involves three steps first recognition of

The antigen fragment by the t-cell receptor secondly provision of co-stimulatory signals by the antigen presenting cell telling the t cell in a way of speaking that these antigen fragments are originating from a pathogen and thirdly the production of the t cell growth hormone interleukin 2 resulting in dna synthesis and cell proliferation as a result the number of t

Cells that can respond to the antigen fragments increases from an insignificant handful to several hundreds of thousands this proliferation of activated t cell clones is called clonal expansion and it is essential to mount an adequate effector an in-memory response colonial proliferation of activated b-cells occurs in the germinal center of the lymph nodes through

A process of somatic hypermutation and clonal selection of proliferating b-cells the antigen binding site of the b-cell receptor is tailored further for the best fitting antibodies most immunosuppressive drugs severely hamper this clonal proliferation by targeting any of the steps involved in the activation and proliferation of t cells for example the calcineurin

Inhibitors cyclosporine and tacrolimus inhibit the intracellular signal of the antigen-recognizing t cell receptor balada cept a fusion protein containing ctla-4 and the fc fragment of adg-1 inhibits d cell co stimulation by the cda t cd28 interaction and mycophenolate acid is a fibrin cyclophosphamate emitter thrax a block cell proliferation by inhibiting dna

Synthesis especially last group of drugs could also severely affect b cell proliferation the net state of immunosuppression is most pronounced during the first year after transplantation anti-rejection therapy adds to this inverse of graft state because of the additional toxic effect of high-dose corticosteroids on lymphocytes or through cell depletion by atg anti

Cd20 or anti c d 50 to monoclonal antibodies now let’s go back to our case study we now know that mofa to mycophenolate will severely hamper clonal proliferation of both t and b cells that have recognized the hepatitis a antigen fragments although safe primary vaccination with hepatitis a vaccine will not lead to protective antibodies so how could we protect this

Patient against hepatitis a in a different way next time when the same vaccine is administered it will be the memory t and b cells that proliferate upon recognition of the antigen these memory cells are much more numerous and are more ready to react upon antigen recognition than the antigen naive cells at the first vaccination this results in a rapid and vigorous

Response called secondary immune response immunosuppressive drugs inhibit clonal expansion of memory cells in the same way as described before and as a result antibody levels will be lower and duration of protection shorter compared to a normal secondary immune response now let’s summarize what we have discussed so far clonal expansion of item naive or memory t

And b cells is essential to acquire sufficient numbers of effector memory cells for an effective immune response after vaccination most immunosuppressive drugs prevent this response from happening by blocking this expansion and as a result antibody responses of the primary vaccination will be often poor to non-existent responses after revaccination will be reduced

But still can be effective one important conclude that can be drawn from this lecture is that an update of childhood and travel vaccinations should occur before transplantation as early as possible immunocompetent pre transplantation recipients should be vaccinated or have proof of serial protection against measles mumps rubella varicella and inactivated vaccines

As you can find on the table if travel to yellow and fever endemic regions is highly desirable in the future vaccination should be considered as well after transplantation vaccination is likely to be ineffective during the first year as the net state of immune suppression is most pronounced during this period after the first year year leary vaccination against

Influenza is advised efficacy however may be limited especially if murphy teal mycophenolate is part of the immunosuppressive regimen you

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Honours Track: Vaccination and transplantation By Centre for Innovation – Leiden University