Research

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Anna  Aldovini, MD

Anna Aldovini
Department:
Medicine Research
Division
Infectious Diseases Research
Hospital Title:
Research Associate
Academic Title:
Associate Professor of Pediatrics, Harvard Medical School
Research Focus Area:
HIV Biology
Contact Via Email
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Research Overview

Anna Aldovini has a long-standing interest in the molecular biology of HIV and AIDS. The two goals of the laboratory are to improve understanding of HIV host-pathogen interactions and to develop new approaches to HIV/AIDS vaccines. Her studies in the area of HIV host-pathogen interactions are focused on how the virus affects host cell biology and progression to AIDS. 

The approaches to vaccine development that have emerged from her laboratory include the identification of non-infectious viral mutants and their use as DNA vaccines for mucosal immunization. The long term goal in the area of HIV host-pathogen interactions is to understand the response to HIV-1 infection in the major target cells for this virus: dendritic cells, macrophages and T cells. 

Her laboratory explored the effects of HIV-1 and its Tat transactivator on primary antigen-presenting cells such as immature dendritic cells using DNA microarray analysis and functional assays and found that HIV-1 infection or Tat expression induces interferon-responsive genes in these cells without inducing maturation. Chemokines that recruit activated T-cells and macrophages, the ultimate target cells for the virus, were among the dendritic cell gene products induced by HIV-1 and Tat. 

Chemokine induction was shown to occurs also during retroviral infection in vivo. These results reveal a novel function for HIV-1 Tat, namely the reprogramming of host dendritic cell gene expression to facilitate expansion of the infection. The goal of AIDS vaccine research is to establish an immunization regimen capable of stimulating both systemic and mucosal humoral and cell mediated immunity. 

Ongoing experiments are evaluating the effectiveness of mucosal DNA vaccination administered via different routes, how vaccine-induced immunity can be improved, and how an immunization regimen that involves different mucosal and systemic routes can provide high levels of systemic and mucosal responses within the same animal and contribute to protection from AIDS. The results of should be important not only for an AIDS vaccine development but also for the development of DNA vaccines for other mucosal pathogens. 

About Dr. Aldovini

Dr. Aldovini obtained her M.D. from the University of Padua Medical School, Italy, where she also did her residency in Oncology. Subsequently she was a Fogarty Fellow at the N.I.H. in Bethesda, MD, and then a Research Scientist at the Whitehead Institute, Cambridge, MA.

Publications

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  1. Aldovini A. Mucosal Vaccination for Prevention of HIV Infection and AIDS. Curr HIV Res. 2016; 14(3):247-59.
  2. Manrique M, Kozlowski PA, Cobo-Molinos A, Wang SW, Wilson RL, Martinez-Viedma Mdel P, Montefiori DC, Carville A, Aldovini A. Resistance to infection, early and persistent suppression of simian immunodeficiency virus SIVmac251 viremia, and significant reduction of tissue viral burden after mucosal vaccination in female rhesus macaques. J Virol. 2014 Jan; 88(1):212-24.
  3. Manrique M, Kozlowski PA, Cobo-Molinos A, Wang SW, Wilson RL, Montefiori DC, Carville A, Aldovini A. Immunogenicity of a vaccine regimen composed of simian immunodeficiency virus DNA, rMVA, and viral particles administered to female rhesus macaques via four different mucosal routes. J Virol. 2013 Apr; 87(8):4738-50.
  4. Manrique M, Kozlowski PA, Cobo-Molinos A, Wang SW, Wilson RL, Montefiori DC, Mansfield KG, Carville A, Aldovini A. Long-term control of simian immunodeficiency virus mac251 viremia to undetectable levels in half of infected female rhesus macaques nasally vaccinated with simian immunodeficiency virus DNA/recombinant modified vaccinia virus Ankara. J Immunol. 2011 Mar 15; 186(6):3581-93.
  5. Manrique M, Kozlowski PA, Wang SW, Wilson RL, Micewicz E, Montefiori DC, Mansfield KG, Carville A, Aldovini A. Nasal DNA-MVA SIV vaccination provides more significant protection from progression to AIDS than a similar intramuscular vaccination. Mucosal Immunol. 2009 Nov; 2(6):536-50.
  6. Abbadessa G, Accolla R, Aiuti F, Albini A, Aldovini A, Alfano M, Antonelli G, Bartholomew C, Bentwich Z, Bertazzoni U, Berzofsky JA, Biberfeld P, Boeri E, Buonaguro L, Buonaguro FM, Bukrinsky M, Burny A, Caruso A, Cassol S, Chandra P, Ceccherini-Nelli L, Chieco-Bianchi L, Clerici M, Colombini-Hatch S, de Giuli Morghen C, de Maria A, de Rossi A, Dierich M, Della-Favera R, Dolei A, Douek D, Erfle V, Felber B, Fiorentini S, Franchini G, Gershoni JM, Gotch F, Green P, Greene WC, Hall W, Haseltine W, Jacobson S, Kallings LO, Kalyanaraman VS, Katinger H, Khalili K, Klein G, Klein E, Klotman M, Klotman P, Kotler M, Kurth R, Lafeuillade A, La Placa M, Lewis J, Lillo F, Lisziewicz J, Lomonico A, Lopalco L, Lori F, Lusso P, Macchi B, Malim M, Margolis L, Markham PD, McClure M, Miller N, Mingari MC, Moretta L, Noonan D, O'Brien S, Okamoto T, Pal R, Palese P, Panet A, Pantaleo G, Pavlakis G, Pistello M, Plotkin S, Poli G, Pomerantz R, Radaelli A, Robertguroff M, Roederer M, Sarngadharan MG, Schols D, Secchiero P, Shearer G, Siccardi A, Stevenson M, Svoboda J, Tartaglia J, Torelli G, Tornesello ML, Tschachler E, Vaccarezza M, Vallbracht A, van Lunzen J, Varnier O, Vicenzi E, von Melchner H, Witz I, Zagury D, Zagury JF, Zauli G, Zipeto D. Unsung hero Robert C. Gallo. Science. 2009 Jan 9; 323(5911):206-7.
  7. Wang SW, Bertley FM, Kozlowski PA, Herrmann L, Manson K, Mazzara G, Piatak M, Johnson RP, Carville A, Mansfield K, Aldovini A. An SHIV DNA/MVA rectal vaccination in macaques provides systemic and mucosal virus-specific responses and protection against AIDS. AIDS Res Hum Retroviruses. 2004 Aug; 20(8):846-59.
  8. Bertley FM, Kozlowski PA, Wang SW, Chappelle J, Patel J, Sonuyi O, Mazzara G, Montefiori D, Carville A, Mansfield KG, Aldovini A. Control of simian/human immunodeficiency virus viremia and disease progression after IL-2-augmented DNA-modified vaccinia virus Ankara nasal vaccination in nonhuman primates. J Immunol. 2004 Mar 15; 172(6):3745-57.
  9. Wang SW, Noonan K, Aldovini A. Nucleocapsid-RNA interactions are essential to structural stability but not to assembly of retroviruses. J Virol. 2004 Jan; 78(2):716-23.
  10. Patel J, Wang SW, Izmailova E, Aldovini A. The simian immunodeficiency virus 5' untranslated leader sequence plays a role in intracellular viral protein accumulation and in RNA packaging. J Virol. 2003 Jun; 77(11):6284-92.
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  12. Izmailova E, Bertley FM, Huang Q, Makori N, Miller CJ, Young RA, Aldovini A. HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages. Nat Med. 2003 Feb; 9(2):191-7.
  13. Wang SW, Aldovini A. RNA incorporation is critical for retroviral particle integrity after cell membrane assembly of Gag complexes. J Virol. 2002 Dec; 76(23):11853-65.
  14. Izmailova E, Aldovini A. Functional analysis of the murine sarcoma virus RNA packaging sequence. J Virol. 2002 May; 76(9):4643-8.
  15. Krogstad P, Geng YZ, Rey O, Canon J, Ibarrondo FJ, Ackerson B, Patel J, Aldovini A. Human immunodeficiency virus nucleocapsid protein polymorphisms modulate the infectivity of RNA packaging mutants. Virology. 2002 Mar 15; 294(2):282-8.
  16. Migliore G, Rossi E, Aldovini A, Mudu P, Alderisio M, Giovagnoli MR, Fabiano A, Morosini PL, Branca M. Variation in the assessment of adequacy in cervical smears. Cytopathology. 2001 Dec; 12(6):377-82.
  17. Branca M, Rossi E, Cedri C, Migliore G, Cedri S, Aldovini A, Leoncini L, Bonelli L, Montanari G, Navone R. [Personnel training for a population screening program for cervical carcinoma]. Pathologica. 2001 Jun; 93(3):233-41.
  18. Wang SW, Kozlowski PA, Schmelz G, Manson K, Wyand MS, Glickman R, Montefiori D, Lifson JD, Johnson RP, Neutra MR, Aldovini A. Effective induction of simian immunodeficiency virus-specific systemic and mucosal immune responses in primates by vaccination with proviral DNA producing intact but noninfectious virions. J Virol. 2000 Nov; 74(22):10514-22.
  19. Jabbar IA, Fernando GJ, Saunders N, Aldovini A, Young R, Malcolm K, Frazer IH. Immune responses induced by BCG recombinant for human papillomavirus L1 and E7 proteins. Vaccine. 2000 May 8; 18(22):2444-53.
  20. Leung NJ, Aldovini A, Young R, Jarvis MA, Smith JM, Meyer D, Anderson DE, Carlos MP, Gardner MB, Torres JV. The kinetics of specific immune responses in rhesus monkeys inoculated with live recombinant BCG expressing SIV Gag, Pol, Env, and Nef proteins. Virology. 2000 Mar 1; 268(1):94-103.
  21. Poon DT, Li G, Aldovini A. Nucleocapsid and matrix protein contributions to selective human immunodeficiency virus type 1 genomic RNA packaging. J Virol. 1998 Mar; 72(3):1983-93.
  22. Coggi G, Bulfamante G, Romeo M, Falleni M, Aldovini A, Cirillo G, Federico D, Roncalli M. Impact of the Pathfinder in a cytology laboratory. Acta Cytol. 1997 Jan-Feb; 41(1):166-72.
  23. Poon DT, Wu J, Aldovini A. Charged amino acid residues of human immunodeficiency virus type 1 nucleocapsid p7 protein involved in RNA packaging and infectivity. J Virol. 1996 Oct; 70(10):6607-16.
  24. Murray PJ, Aldovini A, Young RA. Manipulation and potentiation of antimycobacterial immunity using recombinant bacille Calmette-Guérin strains that secrete cytokines. Proc Natl Acad Sci U S A. 1996 Jan 23; 93(2):934-9.
  25. Tsomides TJ, Aldovini A, Johnson RP, Walker BD, Young RA, Eisen HN. Naturally processed viral peptides recognized by cytotoxic T lymphocytes on cells chronically infected by human immunodeficiency virus type 1. J Exp Med. 1994 Oct 1; 180(4):1283-93.
  26. O'Donnell MA, Aldovini A, Duda RB, Yang H, Szilvasi A, Young RA, DeWolf WC. Recombinant Mycobacterium bovis BCG secreting functional interleukin-2 enhances gamma interferon production by splenocytes. Infect Immun. 1994 Jun; 62(6):2508-14.
  27. Aldovini A, Husson RN, Young RA. The uraA locus and homologous recombination in Mycobacterium bovis BCG. J Bacteriol. 1993 Nov; 175(22):7282-9.
  28. Aldovini A, Young RA. Humoral and cell-mediated immune responses to live recombinant BCG-HIV vaccines. Nature. 1991 Jun 6; 351(6326):479-82.
  29. Aldovini A, Young RA, Palker TJ. New AIDS vaccine candidates: antigen delivery and design. AIDS. 1991; 5 Suppl 2:S151-8.
  30. Yamamoto H, Miller MD, Tsubota H, Watkins DI, Mazzara GP, Stallard V, Panicali DL, Aldovini A, Young RA, Letvin NL. Studies of cloned simian immunodeficiency virus-specific T lymphocytes. gag-specific cytotoxic T lymphocytes exhibit a restricted epitope specificity. J Immunol. 1990 May 1; 144(9):3385-91.
  31. Aldovini A, Young RA. Mutations of RNA and protein sequences involved in human immunodeficiency virus type 1 packaging result in production of noninfectious virus. J Virol. 1990 May; 64(5):1920-6.
  32. Aldovini A, Young RA. Development of a BCG recombinant vehicle for candidate AIDS vaccines. Int Rev Immunol. 1990; 7(1):79-83.
  33. Walker BD, Flexner C, Birch-Limberger K, Fisher L, Paradis TJ, Aldovini A, Young R, Moss B, Schooley RT. Long-term culture and fine specificity of human cytotoxic T-lymphocyte clones reactive with human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1989 Dec; 86(23):9514-8.
  34. Gurgo C, Guo HG, Franchini G, Aldovini A, Collalti E, Farrell K, Wong-Staal F, Gallo RC, Reitz MS. Envelope sequences of two new United States HIV-1 isolates. Virology. 1988 Jun; 164(2):531-6.
  35. Franchini G, Robert-Guroff M, Aldovini A, Kan NC, Wong-Staal F. Spectrum of natural antibodies against five HTLV-III antigens in infected individuals: correlation of antibody prevalence with clinical status. Blood. 1987 Feb; 69(2):437-41.
  36. Feinberg MB, Jarrett RF, Aldovini A, Gallo RC, Wong-Staal F. HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA. Cell. 1986 Sep 12; 46(6):807-17.
  37. Aldovini A, Debouck C, Feinberg MB, Rosenberg M, Arya SK, Wong-Staal F. Synthesis of the complete trans-activation gene product of human T-lymphotropic virus type III in Escherichia coli: demonstration of immunogenicity in vivo and expression in vitro. Proc Natl Acad Sci U S A. 1986 Sep; 83(18):6672-6.
  38. De Rossi A, Franchini G, Aldovini A, Del Mistro A, Chieco-Bianchi L, Gallo RC, Wong-Staal F. Differential response to the cytopathic effects of human T-cell lymphotropic virus type III (HTLV-III) superinfection in T4+ (helper) and T8+ (suppressor) T-cell clones transformed by HTLV-I. Proc Natl Acad Sci U S A. 1986 Jun; 83(12):4297-301.
  39. Fisher AG, Feinberg MB, Josephs SF, Harper ME, Marselle LM, Reyes G, Gonda MA, Aldovini A, Debouk C, Gallo RC, et al. The trans-activator gene of HTLV-III is essential for virus replication. Nature. 1986 Mar 27-Apr 2; 320(6060):367-71.
  40. Aldovini A, De Rossi A, Feinberg MB, Wong-Staal F, Franchini G. Molecular analysis of a deletion mutant provirus of type I human T-cell lymphotropic virus: evidence for a doubly spliced x-lor mRNA. Proc Natl Acad Sci U S A. 1986 Jan; 83(1):38-42.
  41. Del Mistro A, De Rossi A, Aldovini A, Salmi R, Chieco-Bianchi L. Immortalization of human T lymphocytes by HTLV-I: phenotypic characteristics of target cells and kinetics of virus integration and expression. Leuk Res. 1986; 10(9):1109-20.
  42. Sodroski JG, Goh WC, Rosen CA, Salahuddin SZ, Aldovini A, Franchini G, Wong-Staal F, Gallo RC, Sugamura K, Hinuma Y, et al. trans-Activation of the human T-cell leukemia virus long terminal repeat correlates with expression of the x-lor protein. J Virol. 1985 Sep; 55(3):831-5.
  43. de Rossi A, Aldovini A, Franchini G, Mann D, Gallo RC, Wong-Staal F. Clonal selection of T lymphocytes infected by cell-free human T-cell leukemia/lymphoma virus type I: parameters of virus integration and expression. Virology. 1985 Jun; 143(2):640-5.
  44. Chieco-Bianchi L, Aldovini A, Ronchese F, De Rossi A, Majone F, Montaldi A, Levis AG. Short- and long-term studies on chemical carcinogenesis in BALB/Mo mice. Toxicol Pathol. 1984; 12(4):361-8.
  45. Aldovini A, Ronchese F. Different susceptibility of BALB/Mo and BALB/c mice to cytogenetic damage induced by urethan. Tumori. 1983 Oct 31; 69(5):387-90.
  46. Kim N, Kukkonen S, Gupta S, Aldovini A. Association of Tat with promoters of PTEN and PP2A subunits is key to transcriptional activation of apoptotic pathways in HIV-infected CD4+ T cells. PLoS Pathog. 2010 Sep 16; 6(9):e1001103.
  47. Manrique M, Micewicz E, Kozlowski PA, Wang SW, Aurora D, Wilson RL, Ghebremichael M, Mazzara G, Montefiori D, Carville A, Mansfield KG, Aldovini A. DNA-MVA vaccine protection after X4 SHIV challenge in macaques correlates with day-of-challenge antiviral CD4+ cell-mediated immunity levels and postchallenge preservation of CD4+ T cell memory. AIDS Res Hum Retroviruses. 2008 Mar; 24(3):505-19.
  48. Kim N, Dabrowska A, Jenner RG, Aldovini A. Human and simian immunodeficiency virus-mediated upregulation of the apoptotic factor TRAIL occurs in antigen-presenting cells from AIDS-susceptible but not from AIDS-resistant species. J Virol. 2007 Jul; 81(14):7584-97.
  49. Dabrowska A, Kim N, Aldovini A. Tat-induced FOXO3a is a key mediator of apoptosis in HIV-1-infected human CD4+ T lymphocytes. J Immunol. 2008 Dec 15; 181(12):8460-77.
  50. Kim N, Kukkonen S, Martinez-Viedma Mdel P, Gupta S, Aldovini A. Tat engagement of p38 MAP kinase and IRF7 pathways leads to activation of interferon-stimulated genes in antigen-presenting cells. Blood. 2013 May 16; 121(20):4090-100.
  51. Kukkonen S, Martinez-Viedma Mdel P, Kim N, Manrique M, Aldovini A. HIV-1 Tat second exon limits the extent of Tat-mediated modulation of interferon-stimulated genes in antigen presenting cells. Retrovirology. 2014 Apr 17; 11:30.
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