Perhaps vaccines must be engineered to delete epitopes that could interfere with all the desired target response (148). As a different example, provided the observed epitope-dependent heterologous immunity reported and discussed above between IAV and HCV (68,155), would it not be wise to delete the cross-reactive epitope from any live HCV vaccine? The damaging effects of heterologous immunity should, naturally, be balanced with its constructive effects. Mouse model studies have indicated that most of the time heterologous immunity is really a fantastic point for the host (Fig. 1), in that it generally leads to additional speedy clearance from the virus and, in reality, can reduce mortality when the host is exposed to ordinarily lethal doses of virus (96). Together with the collection of the appropriate cross-reactive epitopes, there probably could possibly be manufactured a vaccine that would give fantastic protective immunity but not immunopathology against a wide wide variety of pathogens.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThis work was supported by Usa National Institutes of Wellness (NIH) Investigation Grants AI017672, AI081675, AI073871, AI46692, AI046578, AI049320, AI054455, and AI073540. The opinions expressed are these of your authors gjhs.v8n9p44 and not necessarily these of the NIH. We thank Keith Daniels for enable using the artwork and acknowledge the unpublished study contributions of Alex Chen, Shalyn Clute, Markus Cornberg, Keith Daniels, Anke Kraft, Siwei Nie, Levi Watkin, and Myriam Wlodarczyk.Reference List1. Clark IA. Heterologous immunity revisited. Parasitology. 2001; 122 (Suppl):S51 59. [PubMed: OTX-015 11442196] two. Selin LK, Varga SM, Wong IC, Welsh RM. Protective heterologous antiviral immunity and enhanced immunopathogenesis mediated by memory T cell populations. J Exp Med. 1998; 188:1705?715. [PubMed: 9802982] three. Welsh RM, Selin LK. No one is naive: the significance of heterologous T-cell immunity. Nat Rev Immunol. 2002; two:417?26. [PubMed: 12093008] four. Mathurin KS, Martens GW, Kornfeld H, Welsh RM. CD4 T-cell-mediated heterologous immunity involving mycobacteria and poxviruses. J Virol. 2009; 83:3528?539. [PubMed: 19193795] 5. Mackaness GB. The immunological basis of acquired cellular resistance. J Exp Med. 1964; 120:105?20. [PubMed: 14194388] six. Chen HD, Fraire AE, Joris I, Welsh RM, Selin LK. Precise history of heterologous virus infections epjc/s10052-015-3267-2 determines antiviral immunity and immunopathology within the lung. Am J Pathol. 2003; 163:1341?1355. [PubMed: 14507643] 7. Walzl G, Tafuro S, Moss P, Openshaw PJ, Hussell T. Influenza virus lung infection protects from respiratory syncitial virus-induced immunopathology. J Exp Med. 2000; 192:1317?326. [PubMed: 11067880] eight. Aaby P, Samb B, Simondon F, Seck AM, Knudsen K, Whittle H. Non-specific beneficial effect of measles immunisation:evaluation of mortality studies from creating countries. Brit Med J. 1995; 311:481?85. [PubMed: 7647643] 9. Kristensen I, Aaby P, Jensen H. Routine vaccinations and kid survival: comply with up study in GuineaBissau, West Africa. BMJ. 2000; 321:1435?438. [PubMed: 11110734] 10. Roth A, et al. BCG vaccination scar linked with superior childhood survival in Guinea-Bissau. Int J Epidemiol. 2005; 34:540?47. [PubMed: 15659474]Immunol Rev. Author manuscript; readily available in PMC 2011 May 1.Welsh et al.Page11. Roth AE, Stensballe LG, Garly ML, Aaby P. Beneficial non-targeted effects of BCG–ethical implications for the coming introduction of new TB vaccines. Tub.