Infection-enhancing antibodies

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As antibody-dependent enhancement (Engl. Antibody dependent enhancement , ADE ) are antibodies referred that to the surface of viruses bind, but does not neutralize, but lead to improved uptake of the virus into a cell, and thus the growth and spread favoring the virus. Infection-enhancing antibodies promote immune pathogenesis and are a potential hazard in vaccine development.

properties

Infection-intensifying antibodies are formed in the case of a first infection with some viruses and only cause a more severe course of the disease in the event of a second infection with the same or a similar subtype of the virus. This mechanism considerably limits the possibility of vaccination with some viruses, since the initial infection in this case is imitated by administering a vaccine for active immunization and infection-enhancing antibodies can be formed. Hyperimmunoglobulins for passive immunization can also contain infection-enhancing antibodies and also cause the opposite effect.

The phenomenon of ADE was first observed in 1979 in infections of rhesus monkeys with various subtypes of dengue virus , which had previously been administered antibodies directed against dengue virus as a passive immunization. The cause of the infection-intensifying effect is the formation of poorly or non-neutralizing antibodies in the case of an infection with one of the four subtypes of the dengue virus or a too low concentration of neutralizing antibodies. In particular, the cross-reacting antibodies that are generated against epitopes of the E protein of dengue viruses show an infection-intensifying effect. For example, if antibodies are formed after infection with subtype 1, they are able to prevent renewed infection with subtype 1 and neutralize the viruses. If an infection with a very similar subtype 2 occurs, the antibodies formed against subtype 1 do not neutralize subtype 2, which means that not all surface proteins of a virion are covered by antibodies. The viruses now bind the IgG antibodies with their Fab fragment , while the Fc fragment points outwards. This Fc fragment is bound by the Fc receptors of the macrophages and monocytes and an uptake of the viruses and infection of these cells is initiated.

The infection-intensifying effect of specific antibodies in dengue fever makes the development of classic dengue virus vaccines considerably more difficult .

Infection-enhancing antibodies are also seen in infectious peritonitis in cats when reinfections with the two serotypes of the feline coronavirus occur. The effect also occurs in reinfections with the same serotype. ADE is also observed in infections with picornaviruses and especially in Coxsackievirus B infections, a connection with post -infectious autoimmune diseases is being discussed. In the cell culture system there are indications of ADE in members of the Filoviridae such as Marburg virus and Ebola virus , which is an important indication of the pathogenesis that is still unexplained in detail. Influenza virus ADE has been described in pigs with antibodies that bind near the HA 2 fusion domain .

literature

  • M. Recker et al .: Immunological serotype interactions and their effect on the epidemiological pattern of dengue . In: Proceedings of the Royal Society B: Biological Sciences. (Proc Biol Sci.) July 22, 2009, Volume 276, No. 1667, pp. 2541-2548. doi: 10.1098 / rspb.2009.0331 , PMID 19369266 , PMC 2684681 (free full text).

Individual evidence

  1. ^ Sol M. Cancel Tirado, Kyoung-Jin Yoon: Antibody-dependent Enhancement of Virus Infection and Disease. In: Viral Immunology. Volume 16, 2003, pp. 69-86, PMID 12725690 .
  2. ↑ SB Halstead: In vivo enhancement of dengue virus infection in rhesus monkeys by passively transferred antibody. In: The Journal of Infectious Diseases. (J. Infect. Dis.) 1979, Vol. 140, No. 4, pp. 527-533, PMID 117061 .
  3. ↑ PH Lambert, DM Ambrosino, SR Andersen et al .: Consensus summary report for CEPI / BC March 12-13, 2020 meeting: Assessment of risk of disease enhancement with COVID-19 vaccines. In: Vaccine . [electronic publication before printing] May 2020, doi : 10.1016 / j.vaccine.2020.05.064 , PMID 32507409 , PMC 7247514 (free full text).
  4. ↑ JR Stephenson: Understanding dengue pathogenesis: implications for vaccine design. In: Bulletin of the World Health Organization. 2005, Volume 83, No. 4, pp. 308-814 (Review), PMID 15868023 ( full text ; PDF file; 621 kB).
  5. ↑ T. Takano et al .: Antibody-dependent enhancement occurs upon re-infection with the identical serotype virus in feline infectious peritonitis virus infection. In: Journal of Veterinary Medical Science. (J. Vet. Med. Sci.) 2008, Vol. 70, No. 12, pp. 1315-1321, PMID 19122397 .
  6. ↑ P. Sauter, D. Hober D: Mechanisms and results of the antibody-dependent enhancement of viral infections and role in the pathogenesis of coxsackievirus B-induced diseases. In: Microbes and Infection. 2009, Vol. 1, No. 4, pp. 443-451, PMID 19399964 .
  7. ↑ E. Nakayama et al .: Antibody-dependent enhancement of Marburg virus infection . In: The Journal of Infectious Diseases. (J. Infect. Dis.) 2011, Volume 204, Supplement 3, pp. 978-985, PMID 21987779 .
  8. ↑ S. Khurana, CL Loving, J. Manischewitz, LR King, PC Gauger, J. Henningson, AL Vincent, H. Golding: Vaccine-Induced Anti-HA2 Antibodies Promote Virus Fusion and Enhance Influenza Virus Respiratory Disease. In: Science Translational Medicine. Volume 5, 2013, pp. 200ra114-200ra114, doi: 10.1126 / scitranslmed.3006366 .