Entrevistas ImunoFoz2011 - Rudolph Zinkernagel

SBlogI entrevista:

Dr. Rudolph M. Zinkernagel

Universidade de Zurique, Suiça

SBlogI - What is the theme of your lecture at ImunoFoz 2011?

Zinkernagel, R. M. -  I shall talk about the misuse of words, that give us the illusion of understanding biological phenomena such as protection by vaccines or immunological memory. 

SBlogI - What is the main finding or conclusion that will be emphasized?

Zinkernagel, R. M. -  The main conclusion will be that, while immunological memory exists as an experimental artefact in immunological laboratories, this does not correlate and cannot explain protection by vaccines or by previous infections. The reason for the discrepancy is, that immunologists use assays that are independent of protection to monitor immune responses. In addition, in most cases epidemiological control of vaccine efficiencies independent of ongoing infections in the population can usually not be done. Very recent developments however suggest, that except for persisting vaccines or infections (e.g. measles), reencounter of the antigen or the infection is mandatory for long term protection. We have shown this experimentally. There is now evidence also epidemiologically, that protection fades away in a population, that has not sufficient levels of circulating infectious agent or of a live attenuated vaccine.  

SBlogI - What is the significance of this finding? 

Zinkernagel, R. M. - The significance of these findings is of course, that vaccines as we are used to at the moment, will soon loose efficacy, because of fading additional exposure to epidemiologically active infections. Therefore revaccinations will have to be much more frequent. 

SBlogI - What are the future perspectives in this area?

Zinkernagel, R. M. - The future in the area could be that vaccine carriers that persist at low levels in the host without causing immunopathology, may be very attractive to solve this problem of necessary repeated reexposure. Since this is also a primary requirement for any vaccine against TB, HIV or malaria, this may be crucial. 

SBlogI - What are the challenges in this area? Are there controversies? Opponent hypotheses?

Zinkernagel, R. M. -  Any persistent vaccine may cause immunopathology and therefore cause clinical problems. In addition, any persisting virus or vaccine carrier may recombine with endogenous retroviruses at some level and potentially cause infections. Of course, there are many controversies, because more than 90 % of immunologists think that immunological memory is responsible for vaccine action, so most immunologists believe, that a vaccine against TB or HIV is readily possible. But it has been shown, that a vaccine against TB depends on persistence of the vaccine (e.g. BCG) or that the variability of HIV or malaria prevents an efficacious vaccine to be developed, unless one combines 10’000 to perhaps 10⁶ variants into a vaccine or generates new mutating vaccines. Again, the potential problems might be that such vaccines recreate the old disease or something similar and therefore will be a problem. 

SBlogI - Any suggestions for background reading?

Zinkernagel, R. M. - Background reading suggestions are given in the following list:

1.         Zinkernagel RM, Ehl S, Aichele P, Oehen S, Kundig T and Hengartner H (1997) Antigen localisation regulates immune responses in a dose- and time-dependent fashion: a geographical view of immune reactivity. Immunol Rev 156:199-209
2.         Zinkernagel RM (2001) Maternal antibodies, childhood infections, and autoimmune diseases. N Engl J Med 345:1331-1335
3.         Zinkernagel RM (2002) On differences between immunity and immunological memory. Curr Opin Immunol 14:523-536
4.         Zinkernagel RM (2003) On natural and artificial vaccinations. Annu Rev Immunol 21:515-546
5.         Pericin M, Althage A, Freigang S, Hengartner H, Rolland E, Dupraz P, Thorens B, Aebischer P and Zinkernagel RM (2002) Allogeneic beta-islet cells correct diabetes and resist immune rejection. Proc Natl Acad Sci U S A 99:8203-8206
6.         Zinkernagel RM and Hengartner H (2004) On immunity against infections and vaccines: credo 2004. Scand J Immunol 60:9-13
7.         Zinkernagel RM (2004) On 'reactivity' versus 'tolerance'. Immunol Cell Biol 82:343-352
8.         Zinkernagel RM and Hengartner H (2006) Protective 'immunity' by pre-existent neutralizing antibody titers and preactivated T cells but not by so-called 'immunological memory'. Immunol Rev 211:310-319 
9.         Zinkernagel R (2007) On observing and analyzing disease versus signals. Nat Immunol 8:8-10