M.D. 09/1977- 05/1983 North-Osetian State School of Medicine, Russia
Ph.D. 09/1983- 05/1986 Chelyabinsk State School of Medicine, Department of Microbiology and Immunology, Russia
D.Sc. 09/1990- 09/1993 Institute of Immunology, Ministry of Public Health, Russia, Moscow, Russia and Mechnikov Research Institute of Vaccines and Sera, Russian Academy of Medical Sciences (RAMS), Moscow, Russia
09/1990 - 09/1993 Postdoctoral training, Mechnikov Research Institute of Vaccines and Sera, Russian Academy of Medical Sciences (RAMS), Moscow, Russia
09/1993 - 09/1995 Postdoctoral Fellowship, Immunobiology Vaccine Center, University of Alabama, Birmingham, Alabama, USA
12/1996 - 11/2001 Postdoctoral Fellow, Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA
09/1986 - 09/1987 Assistant Professor, Department of Microbiology and Immunology, North-Osetian State School of Medicine, Russia
09/1987 - 09/1989 Associate Professor, Department of Microbiology and Immunology, North-Osetian State School of Medicine, Russia
09/1989 - 09/1990 Professor and Chief Department of Microbiology and Immunology, North-Osetian State School of Medicine, Russia
09/1990 - 09/1993 Section Head, Department of T Cell Differentiation, Institute of Immunology, Moscow, Russia
09/1995 - 12/1996 Instructor, Department of Microbiology, Pathology & Parasitology, North Carolina State University, Raleigh, North Carolina
11/2001 - 11/2006 Senior Staff Scientist, Vaccine Branch, Center for Cancer Research (CCR), National Cancer Institute, National Institutes of Health, Bethesda, Maryland
08/2007 - 09/2010 Principal Scientist, Midwest Research Institute, Frederick, Maryland
Dr. Belyakov‘s area of expertise is in mucosal immunology, basic mechanisms of inflammation, animal models of infection and tumors, viral immunology, pathogen-associated cancers, the immunology of host-pathogen interactions, and development of vaccines against chronic infectious diseases and cancer. He has made significant contributions to elucidating new fundamental principles governing T cell activation, regulation, and effector function. He uses these new fundamental principles to develop more effective mucosal vaccines and immunotherapy strategies for pathogens causing infectious diseases in human and animals (including HIV-1, SIV, Poxvirus, Influenza, Avian Influenza, RSV, Anthrax, and others). Thus far Dr. Belyakov’s career path has been in institutions (NIH intramural, Midwest Research Institute) where grant making was not expected. He has one NIH Intramural AIDS Targeted Antiviral Program grant as Co-PI. Dr. Belyakov’s publication record is outstanding with 70 peer-reviewed publications (30 as first author) as well as 20 invited review articles in high impact journals. Ten of Dr. Belyakov’s papers are considered as classic papers in Immunology and Vaccine development, and every paper from this list was cited over 100 times and some publications are cited over 200 times. He has given 64 invited presentations. He has three patents. Dr. Belyakov’s high level expertise is shown by his peer-review service for more than 25 journals as well as service on six editorials boards. He has significant teaching experience with medical students, Ph.D. students and postdoctoral research fellows for more than 15 years.
Highlights of Dr. Belyakov’s research include demonstration that mucosal immunization with a synthetic, multideterminant HIV peptide construct plus cholera toxin adjuvant induced long-lasting, antigen-specific memory in both the inductive (Peyer’s patch) and effector (lamina propria) mucosal sites, as well as in systemic sites (Belyakov et al. Proc. Natl. Acad.Sci., Vol.95, pp1709-1714, 1998). He presented the first direct demonstration of the importance of mucosal cytotoxic T lymphocytes in protection against mucosal transmission of virus (Belyakov et al. J. Clin. Invest. 1998. Vol.102, pp2072-2081). Mucosal viral transmission was dependent on CD8+ CTL that had to be present in the mucosal site to be effective and systemic CTL were not sufficient. This result has important implications for vaccine development, in that if a vaccine is going to protect against mucosal transmission of virus, it will likely have to induce specific CTL at the mucosal sites of exposure, and not just in the systemic circulation. He also demonstrated that the choice of mucosal adjuvant affects the cytokine enviroment, and the mucosal response and protection can be enhanced by manipulating the cytokine environment with synergistic cytokine combinations incorporated in the vaccine (Belyakov et al. J.Immunol., Vol.165, p.6454-6462, 2000).
He has shown that activated DCs carrying skin-derived antigen also migrate from the skin to immune inductive sites in gut mucosa and present antigen directly to resident lymphocytes (Belyakov et al. J. Clin. Invest. 2004. Vol.113, pp.998-100). In previous studies, he has shown that, at sufficient doses, the protection provided by both modified vaccinia Ankara and NYVAC replication-deficient vaccinia virus, safe in immunocompromised animals, was equivalent to that of the licensed Wyeth vaccine strain against a pathogenic vaccinia virus challenge. For both, antibody was essential to protect against disease, whereas neither effector CD4+ nor CD8+ T cells were necessary or sufficient (Belyakov et al. Proc. Natl. Acad.Sci., Vol.100, pp9458-9463, 2003). Moreover, he demonstrated that a protective adjuvant effect of CpG ODN for a live viral vector vaccine is mediated predominantly by CD8+ T cells responses, but not neutralizing antibody production, and may overcome CD4 deficiency in the induction of protective CD8+ T-cell mediated immunity (Belyakov et al., Journal of Immunology, 2006, Vol.177, pp. 6336-6343).
Recently, his group demonstrated that strategic use of molecular adjuvants can provide better mucosal protection through induction of both innate and adaptive immunity (Sui et al., et al. Proc. Natl. Acad.Sci., Vol.107(21), pp9843-9848, 2010). Their data highlight the importance of both innate and adaptive immunity in effective control of infection by vaccination, and suggest correlates of protection that motivate further study of these parameters. The proposed model provides insights for designing a future HIV vaccine. They have also demonstrated that selective TLR ligand combinations can increase protective efficacy by increasing the quality rather than the quantity of T cell responses (Zhu Q., et al., 2010, Journal of Clinical Investigation, Vol.120(2), pp.607-616). The study revealed that, whereas double combinations of TLR ligands quantitatively expand T cell responses, the triple combination qualitatively strengthens the responses by inducing higher-functional avidity T cells and thus more effectively protects against viral challenge.
1. Belyakov I.M., Derby M.A., Ahlers J.D., Kelsall B.L., Earl P., Moss B., Strober W., & Berzofsky J.A., 1998. Mucosal Immunization with HIV-1 peptide vaccine induces mucosal and systemic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge. Proc. Natl. Acad. Sci. USA, Vol.95, pp.1709-1714.
2. Belyakov I.M., Wyatt L.S., Ahlers J.D., Earl P., Pendleton C.D., Kelsall B.L., Strober W., Moss B., & Berzofsky J.A., 1998. Induction of mucosal CTL response by intrarectal immunization with a replication-deficient recombinant vaccinia virus expressing HIV 89.6 envelope protein. Journal of Virology, Vol.72 (10), pp. 8264-8272.
3. Belyakov I.M., Ahlers J.D., Brandwein B.Y., Earl P., Kelsall B.L., Strober W., Moss B., & Berzofsky J.A., 1998. Local mucosal HIV-specific CD8+ cytotoxic T lymphocytes protect against mucosal transmission of recombinant virus expressing HIV-1 gp160. Enhancement of protection by local administration of IL-12. Journal of Clinical Investigation, Vol.102, pp.2072-2081.
4. Belyakov I.M., Moss B., Strober W., & Berzofsky J.A., 1999. Mucosal vaccination overcomes the barrier to recombinant vaccinia immunization caused by preexisting poxvirus immunity. Proc. Natl. Acad. Sci. USA, Vol.96, pp.4512-4517.
5. Berzofsky J.A., Ahlers J.D., Derby M.A., Pendelton C.D., Arichi T., & Belyakov I.M. 1999. Approaches to improve engineered vaccines for HIV and other viruses that cause chronic infections. Immunological Reviews, Vol.170, pp.151-172.
6. Belyakov I.M., Ahlers J.D., Clements J.D., Strober W., & Berzofsky J.A., 2000. Interplay of cytokines and adjuvants in the regulation of mucosal and systemic HIV-specific CTL. Journal of Immunology, Vol.165, pp.6454-6462.
7. Belyakov I.M., Hel Z, Kelsall B, Kuznetsov V., Ahlers J.D., Nacsa J., Watkins D.I., Altman J, Woodward R, Markham P., Clements J.D., Franchini G., Strober W., & Berzofsky J.A., 2001. Mucosal AIDS Vaccine Reduces Disease and Viral Load in Gut Reservoir and Blood After Mucosal Infection of Macaques. Nature Medicine, Vol.7, pp.1320-1326.
8. Belyakov I.M., Wang J., Koka R., Ahlers J.D., Snyder J.T., Tse R., Cox J., Gibbs J.S., Margulies D., & Berzofsky J.A., 2001. Activating CTL precursors to reveal CTL function without skewing the repertoire by in vitro expansion. European Journal of Immunology, Vol.31, pp. 3557-3566.
9. Ahlers J.D., Belyakov I.M., Thomas E.K., & Berzofsky J.A., 2001. High-affinity T helper epitope induces complementary helper and APC polarization, increased CTL and protection against viral infection. Journal of Clinical Investigation, Vol.108, 1677-1685.
10. Berzofsky J.A., Ahlers J.D., & Belyakov I.M., 2001. Strategies for Designing and Optimizing New Generation Vaccines. Nature Reviews: Immunology, Vol.1 (3), pp.209- 219.
11. Biragyn A., Belyakov I.M., Chow Y.H., Dimitrov D.S., Berzofsky J.A., & Kwak L.W., 2002. DNA vaccines encoding HIV-1 gp120 fusions with proinflammatory chemoattractants induce systemic and mucosal immune responses. Blood, Vol. 100(4), pp1153-1159.
12. Bukreyev A. & Belyakov I.M., 2002. Expression of immunomodulating molecules by recombinant viruses: Can immunogenicity of live virus vaccines be improved? Expert Reviews: Vaccine, Vol.1 (2), pp.233-244.
13. Ahlers J.D., Belyakov I.M., Terabe M., Koka R., Donaldson D., Thomas E.K., & Berzofsky J.A., 2002. A push-pull approach to maximize vaccine efficacy: Abrogating Suppression with an IL-13 inhibitor while augmenting help with granulocyte/ macrophage colony-stimulating factor and CD40L. Proc. Natl. Acad. Sci. USA, Vol.99, pp.13020- 13025.
14. Belyakov I.M., Earl P., Dzutsev A., Kuznetsov V.A., Lemon M., Wyatt L.S., Snyder J.S., Ahlers J.D., Franchini G., Moss B., & Berzofsky J.A., 2003. Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses. Proc. Natl. Acad. Sci. USA, Vol.100 (16), pp.9458-9463.
15. Snyder J.T., Alexander-Miller M.A., Berzofsky J.A., & Belyakov I.M., 2003. Molecular mechanisms and biological significance of CTL avidity. Current HIV Research, Vol.1, pp.287-294.
16. Belyakov I.M., Hammond S.A., Ahlers J.D., Glenn G.M. & Berzofsky J.A., 2004. Transcutaneous immunization induces mucosal CTL and protective immunity by migration of primed skin dendritic cells. Journal of Clinical Investigation, Vol.113 (7), pp.998- 1007.
17. Belyakov I.M., & Berzofsky J.A., 2004. Immunobiology of mucosal HIV infection and the basis for development of a new generation of mucosal AIDS vaccines. Immunity, Vol.20 (3), pp.247-253.
18. Kuznetsov V.A., Stepanov V.S., Berzofsky J.A., & Belyakov I.M., 2004. Assessment of the relative therapeutic effects of vaccines on virus load and immune responses in small groups at several time points: Efficacy of mucosal and subcutaneous polypeptide vaccines in rhesus macaques exposed to SHIV. Journal of Clinical Virology, Vol. 31S, pp. S69- S82.
19. Berzofsky J.A., Terabe M., Oh SK, Belyakov I.M., Ahlers J.D., Janik J., & Morris J., 2004. Progress on new vaccine strategies for the immunotherapy or prevention of cancer. Journal of Clinical Investigation, Vol.113(11), pp.1515-25.
20. Berzofsky J.A., Ahlers J.D., Janik J., Morris J., Oh SK., Terabe M., & Belyakov I.M., 2004. Progress on new vaccine strategies for chronic viral infections. Journal of Clinical Investigation, Vol.114 (4), pp.450-462.
21. Yarilin A.A., & Belyakov I.M., 2004. Cytokines in the thymus: production and biological effects. Current Medicinal Chemistry, Vol.11, pp. 447-464.
22. Belyakov I.M., Ahlers J.D., & Berzofsky J.A., 2004. Mucosal AIDS Vaccines: Current Status and Future Directions. Expert Reviews: Vaccine, Vol. 3(4) Suppl 1, pp.S65-73.
23. Belyakov I.M., Kuznetsov V.A., Kelsall B., Klinman D., Moniuszko M., Lemon M., Markham P.D., Pal P., Clements J.D., Lewis M.G., Strober W., Franchini G., & Berzofsky J.A., 2006. Impact of Vaccine-induced Mucosal High Avidity CD8+ CTL in Delay of AIDS-viral Dissemination from Mucosa. Blood, Vol.107 (8), pp. 3258-3264.
24. Belyakov I.M., Isakov D., Zhu Q., Dzutsev A., Klinman D., & Berzofsky J.A., 2006. Enhancement of CD8+ T cell Immunity in the Lung by CpG ODN Increases Protective Efficacy of a Modified Vaccinia Ankara Vaccine Against Lethal Poxvirus Infection Even in a CD4-Deficient Host. Journal of Immunology, Vol.177, pp. 6336-6343.
25. Belyakov I.M., Isakov D., Zhu Q., Dzutsev A. & Berzofsky J.A., 2007. A Novel Functional CTL Avidity/Activity Compartmentalization to the Site of Mucosal Immunization Contributes to Protection of Macaques Against Simian/Human Immunodeficiency Viral Depletion of Mucosal CD4+ T cells. Journal of Immunology, Vol.178, pp.7211-7221.
26. Belyakov I.M., Kozlowski S., Mage M., Ahlers J.D., Boyd L.F., Margulies D.H. & Berzofsky J.A., 2007. Role of á3 domain of class I MHC molecules in the activation of high and low avidity of CD8+ cytotoxic T lymphocytes. International Immunology, Vol.19 (12); pp.1413-1420; doi: 10.1093/intimm/dxm111.
27. Belyakov I.M. & Ahlers J.D., 2008. Functional CD8+ CTL in Mucosal Sites and HIV Infection: Moving Forward toward a Mucosal AIDS Vaccine. Trends in Immunology, Vol.29(11), pp.574-585. doi:10.1016/j.it.2008.07.010.
28. Zhu Q., Egelston C., Vivekanandhan A., Uematsu S., Akira S., Klinman D.M., Belyakov I.M., & Berzofsky J.A., 2008. Toll-like receptor ligands synergize through distinct dendritic cell pathways to induce T cell responses: implications for vaccines. Proc. Natl. Acad. Sci. USA, Vol.105 (42), pp.16260-16265. Epub 2008 Oct 9. doi:10.1073/pnas.0805325105.
29. Belyakov I.M., Ahlers J.D., Nabel G.J., Moss B., & Berzofsky J.A., 2008. Generation of functionally active HIV-1 specific CD8+ CTL in intestinal mucosa following mucosal, systemic or mixed prime-boost immunization. Virology, Vol.381(1); pp.106-115; doi:10.1016/j.virol.2008.08.019. Epub 2008 Sep 14.
30. Ahlers J.D & Belyakov I.M., 2009. Strategies for Recruitment and Targeting Dendritic Cells for Optimizing HIV Vaccines. Trends in Molecular Medicine, Vol.15(6), pp.263- 274. Epub 2009 May 30.
31. Ahlers J.D & Belyakov I.M., 2009. Strategies for Optimizing Targeting and Delivery of Mucosal HIV Vaccines. European Journal of Immunology, Vol.39(10), pp.2657- 2669.
32. Isakov D., Dzutsev A., Belyakov I.M., & Berzofsky J.A., 2009. Non-equilibrium and Differential Function Between Intraepithelial and Lamina Propria Virus-Specific TCRáâ+CD8áâ+ T Cells in the Small Intestinal Mucosa. Mucosal Immunology, Vol.2(5), pp.450-461. Epub 2009 Jul 1.
33. Belyakov I.M. & Ahlers J.D., 2011. Mucosal Immunity and HIV Infection: Applications for Mucosal AIDS Vaccine Development. Current Topics in Microbiology and Immunology, DOI: 10.1007/82_2010_119. Published online: 04 January 2011.
34. Ahlers J.D & Belyakov I.M., 2010. Memories that Last Forever: Strategies for Optimizing Vaccine T Cell Memory. Blood, Vol.115(9), pp.1678-1689. Epub 2009 Nov 10; DOI 10.1182/blood-2009-06-227546.
35. Belyakov I.M., & Ahlers J.D., 2009. What Role Does the Route of Immunization Play in Generation of Protective Immunity Against Mucosal Pathogens? Journal of Immunology, Vol.183(11), pp.6883-6892. doi:10.4049/jimmunol.0901466.
36. Ahlers J.D & Belyakov I.M., 2010. Lessons Learned from Natural Infection: Focusing in on the Design of Protective T cell Vaccines for HIV/AIDS. Trends in Immunology, Vol.31(3), pp.120-130. Epub 2010 Jan 19. doi:10.1016/j.it.2009.12.003.
37. Zhu Q., Egelston C., Sui Y., Gagnon S., Belyakov I.M., Klinman D.M., & Berzofsky J.A., 2010. Using 3 TLR ligands as a combination adjuvant induces qualitative changes in T-cell responses needed for antiviral protection in mice. Journal of Clinical Investigation, Vol.120(2), pp.607-616. doi: 10.1172/JCI39293. Epub 2010 Jan 25.
38. Sui Y., Zhu Q., Gagnon S., Dzutsev A., Terabe M., Vaccari M., Venzon D., Klinman D., Strober W., Kelsall B., Franchini G., Belyakov I.M., & Berzofsky J.A., 2010. Innate and adaptive immune correlates of vaccine and adjuvant-induced control of mucosal transmission of SIV in macaques. Proc. Natl. Acad. Sci. USA, Vol.107(21), pp.9843- 9848.
39. Ahlers J.D & Belyakov I.M., 2010. Molecular pathways regulating CD4+ T cell differentiation, anergy and memory with implications for vaccines. Trends in Molecular Medicine, Vol.16(10), pp.478-491, doi:10.1016/j.molmed.2010.07.007, published online on 24 August 2010.
40. Ahlers J.D & Belyakov I.M., 2010. New Paradigms for generating effective CD8+ T cell responses against HIV-1/AIDS. Discovery Medicine, Vol.9 (49), pp.528-537.
41. Belyakov I.M. & Ahlers J.D., 2011. Simultaneous approach using systemic, mucosal and transcutaneous routes of immunization for induction of protective mucosal immune responses. Current Medical Chemistry.