Corinna La Rosa, Ph.D.

Corinna La Rosa, Ph.D.

  • Associate Research Professor, Department of Experimental Therapeutics

Corinna La Rosa, Ph.D.

Research Focus :
  • Immune monitoring to evaluate response and assess efficacy of cytomegalovirus (CMV) experimental vaccines in transplant patients
  • Immune mechanisms and biomarkers of primary CMV response in solid organ transplant recipients
  • 2008-present Associate Research Professor - Department of Experimental Therapeutics, City of Hope, Duarte, CA
  • 2004-2008, Assistant Research Scientist, Laboratory of Vaccine Research, City of Hope, Duarte, CA
  • 1997-2004, Senior Research Fellow, Department of Virology, City of Hope, Duarte, CA
  • 1994-1996 Postdoctoral Fellow Department of Molecular, Cellular and Animal Biology, University of Camerino, Italy
  • 1993, University of Pisa, Italy, Ph.D., Biology
  • 1989 - 1993, Graduate student, Department of Molecular, Cellular and Animal Biology, University of Camerino, Italy
  • 1989, University of Camerino, Italy, M.Sc., Biology
  • 1984, Liceo Classico Civitavecchia, Italy, B.A., Classical Studies

CMV peptide vaccine clinical trial

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The crucial element in a peptide vaccine approach is the ability of the cytotoxic T-lymphocyte (CTL) epitope to bind to MHC molecules that are expressed in a major proportion of the population. CMV pp65495-503 CTL epitope is largely recognized among CMV+ HLA-A*0201 individuals. Linking the pan-DR epitope peptide (PADRE) or one of several tetanus TH epitopes to the immunodominant  pp65495-503 CTL epitope induces robust cytotoxic cellular immune responses in HLA-A*0201 transgenic mice. CpG-containing single-stranded DNA added to the fusion peptides dramatically up regulates immune recognition. TH-CTL epitope fusion peptides in combination with CpG ss-ODN is the innovative strategy that we have developed for delivery of a safe CMV immunogen. Our approach is to amplify the CMV-pp65-specific memory CTL response in a transplant donor, by administering the CMV fusion peptides with or without CpG adjuvant.

The vaccines have been produced in collaboration with the National Cancer Institute according to federal c-GMP regulations and the phase I clinical dose-escalation trial has started in the fall of 2006, at our General Clinic Research Center. The trial focuses on demonstrating safety and immunogenicity of PADRE-CMV and Tetanus-CMV vaccines in healthy adults. We have enrolled so far 30% of the volunteers needed to fill the study cohorts, and vaccinated 18 of them. The fusion peptides are safe and well tolerated, and at 2.5 mg of the vaccine dose the levels of CMV-specific CD8+ T-cell producing IFN-gappear to transiently rise. While these encouraging results need to be confirmed on additional volunteers, increased frequencies of these CMV-specific T cell subsets may characterize a successful vaccine response, and be indicative of protection from disease or viremia.

Immunological evaluation of CMV-MVA recombinant vectors

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The highly attenuated modified vaccinia Ankara (MVA) engineered with recombinant genes is being increasingly evaluated as a clinical vaccine for infectious disease and cancer. The attractiveness of MVA for clinical use stems from its efficacy records and pronounced safety, even under conditions of immunosuppression. We have developed recombinant MVA incorporating immunogenic targets of CMV. CMV-MVA vectors stimulate vigorous expansion of CMV-specific CD8+ and CD4+ T cells in CMV+ PBMC, which show minimal alloreactivity and high levels of HLA tetramer binding, cytokine production, and cytotoxicity. Transgenic mice, immunized with CMV-MVA, produce a robust CMV-specific response. The specificity of the vigorous immunologic response to CMV-MVA makes them candidates for clinical evaluation in the context of adoptive immunotherapy or donor vaccination. We have completed a stabilization analysis of a markedly immunogenic MVA candidate vaccine, co-expressing CMV pp65, IE1, IE2 immunodominant antigens. This construct has been selected for a Phase I/II evaluation, and clinical trial batches are going to be soon c-GMP manufactured.

Immunologic correlates of late CMV disease in high-risk liver transplant recipients

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Since there is a critical lack of prognostic tools for early detection of post-transplant CMV disease, the goal of this project is to develop predictive immunological assays to target preventive strategies against symptomatic CMV infection. Our investigation focuses on CMV- recipients (R-) receiving a solid organ transplant from CMV+ donors (D+), who are at the highest risk for life-threatening CMV disease. This study is in collaboration with University of Washington Medical Center. We have found that CMV-specific cell lytic function and IFN-g production are not predictive of CMV disease or viraemia in D+/R- recipients. In contrast, increased expression levels of the pro-apoptotic marker PD-1 are temporally and quantitatively associated with incipient and overt CMV disease, and viraemia in the same patients. PD-1 could be developed as a prognostic tool to predict CMV disease and guide therapeutic interventions. Supported by our novel findings, we are planning to perform a broader longitudinal study with the aim of identifying correlates of protection, which will be instrumental in managing at risk D+/R- patients.

  • Nakamura R, La Rosa C, Longmate J, Drake J, Slape C, Zhou Q, Lampa MG, O'Donnell M, Cai JL, Farol L, Salhotra A, Snyder DS, Aldoss I, Forman SJ, Miller JS, Zaia JA, Diamond DJ. Viraemia, immunogenicity, and survival outcomes of cytomegalovirus chimeric epitope vaccine supplemented with PF03512676 (CMVPepVax) in allogeneic haemopoietic stem-cell transplantation: randomized phase 1b trial. The Lancet. Haematology. 2016; 3(2):e87-98. NIHMSID: NIHMS796160 PubMed [journal] PMID: 26853648, PMCID: PMC4926626
  • Limaye AP, La Rosa C, Longmate J, Diamond DJ. Plasma IL-10 Levels to Guide Antiviral Prophylaxis Prevention of Late-Onset Cytomegalovirus Disease, in High Risk Solid Kidney and Liver Transplant Recipients. Transplantation. 2016; 100(1):210-6. NIHMSID: NIHMS690186 PubMed [journal] PMID: 26680375, PMCID: PMC4685744
  • Wang X, Wong CW, Urak R, Mardiros A, Budde LE, Chang WC, Thomas SH, Brown CE, La Rosa C, Diamond DJ, Jensen MC, Nakamura R, Zaia JA, Forman SJ. CMVpp65 Vaccine Enhances the Antitumor Efficacy of Adoptively Transferred CD19-Redirected CMV-Specific T Cells. Clinical cancer research : an official journal of the American Association for Cancer Research. 2015; 21(13):2993-3002. NIHMSID: NIHMS677258 PubMed [journal] PMID: 25838392, PMCID: PMC4489991
  • Wussow F, Chiuppesi F, Martinez J, Campo J, Johnson E, Flechsig C, Newell M, Tran E, Ortiz J, La Rosa C, Herrmann A, Longmate J, Chakraborty R, Barry PA, Diamond DJ. Human cytomegalovirus vaccine based on the envelope gH/gL  pentamer complex. PLoS pathogens. 2014; 10(11):e1004524. PubMed [journal] PMID: 25412505, PMCID: PMC4239111
  • Nakamura R, La Rosa C, Tsai W, Lacey SF, Srivastava T, Seidel A, Senitzer D, Forman SJ, Diamond DJ. Ex vivo detection of CD8 T cells specific for H-Y minor histocompatibility antigens in allogeneic hematopoietic stem cell transplant  recipients. Transplant immunology. 2014; 30(4):128-35. PubMed [journal] PMID: 24582729
  • Israyelyan A, La Rosa C, Tsai W, Kaltcheva T, Srivastava T, Aquino L, Li J, Kim Y, Palmer J, Streja L, Senitzer D, Zaia JA, Rosenwald A, Forman SJ, Nakamura R, Diamond DJ. Detection and preliminary characterization of CD8+T lymphocytes specific for Wilms' tumor antigen in patients with non-Hodgkin lymphoma. Leukemia & lymphoma. 2013; 54(11):2490-9. NIHMSID: NIHMS498785 PubMed [journal] PMID: 23480492, PMCID: PMC3795970
  • La Rosa C, Longmate J, Lacey SF, Kaltcheva T, Sharan R, Marsano D, Kwon P, Drake J, Williams B, Denison S, Broyer S, Couture L, Nakamura R, Dadwal S, Kelsey MI, Krieg AM, Diamond DJ, Zaia JA. Clinical evaluation of safety and immunogenicity of PADRE-cytomegalovirus (CMV) and tetanus-CMV fusion peptide vaccines with or without PF03512676 adjuvant. The Journal of infectious diseases. 2012; 205(8):1294-304. PubMed [journal] PMID: 22402037, PMCID:   PMC3308906
  • La Rosa C, Diamond DJ. The immune response to human CMV. Future virology. 2012; 7(3):279-293. NIHMSID: NIHMS429188 PubMed [journal] PMID: 23308079, PMCID: PMC3539762
  • La Rosa C, Limaye AP, Krishnan A, Blumstein G, Longmate J, Diamond DJ. Primary response against cytomegalovirus during antiviral prophylaxis with valganciclovir, in solid organ transplant recipients. Transplant international: official journal of the European Society for Organ Transplantation. 2011; 24(9):920-31. NIHMSID: NIHMS423055 PubMed [journal] PMID: 21672050, PMCID: PMC3514504
  • Lacey SF, La Rosa C, Kaltcheva T, Srivastava T, Seidel A, Zhou W, Rawal R, Hagen K, Krishnan A, Longmate J, Andersson HA, St John L, Bhatia R, Pullarkat V, Forman SJ, Cooper LJ, Molldrem J, Diamond DJ. Characterization of immunologic properties of a second HLA-A2 epitope from a granule protease in CML patients and HLA-A2 transgenic mice. Blood. 2011; 118(8):2159-69. PubMed [journal] PMID: 21719601, PMCID: PMC3162352
  • Manuel ER, Wang Z, Li Z, La Rosa C, Zhou W, Diamond DJ. Intergenic region 3 of modified vaccinia ankara is a functional site for insert gene expression and allows for potent antigen-specific immune responses. Virology. 2010; 403(2):155-62. NIHMSID: NIHMS200263 PubMed [journal] PMID: 20471051, PMCID: PMC2879446
  • Krishnan A, Zhou W, Lacey SF, Limaye AP, Diamond DJ, La Rosa C. Programmed death-1 receptor and interleukin-10 in liver transplant recipients at high risk for late cytomegalovirus disease. Transplant infectious disease : an official journal of the Transplantation Society. 2010; 12(4):363-70. NIHMSID: NIHMS238558 PubMed [journal] PMID: 20070620, PMCID: PMC2950160
  • Wang Z, Martinez J, Zhou W, La Rosa C, Srivastava T, Dasgupta A, Rawal R, Li Z, Britt WJ, Diamond D. Modified H5 promoter improves stability of insert genes while maintaining immunogenicity during extended passage of genetically engineered MVA vaccines. Vaccine. 2010; 28(6):1547-57. NIHMSID: NIHMS162053 PubMed [journal] PMID: 19969118, PMCID: PMC2821965
  • Li J, Srivastava T, Rawal R, Manuel E, Isbell D, Tsark W, La Rosa C, Wang Z, Li Z, Barry PA, Hagen KD, Longmate J, Diamond DJ. Mamu-A01/K(b) transgenic and MHC Class I knockout mice as a tool for HIV vaccine development. Virology. 2009; 387(1):16-28. NIHMSID: NIHMS95982 PubMed [journal] PMID: 19249807, PMCID: PMC2667874
  • Krishnan A, Wang Z, Srivastava T, Rawal R, Manchanda P, Diamond DJ, La Rosa C. A novel approach to evaluate the immunogenicity of viral antigens of clinical importance in HLA transgenic murine models. Immunology letters. 2008; 120(1-2):108-16. NIHMSID: NIHMS72547 PubMed [journal] PMID: 18706443, PMCID: PMC2577668
  • Wang Z, Zhou W, Srivastava T, La Rosa C, Mandarino A, Forman SJ, Zaia JA, Britt WJ, Diamond DJ. A fusion protein of HCMV IE1 exon4 and IE2 exon5 stimulates potent cellular immunity in an MVA vaccine vector. Virology. 2008; 377(2):379-90. NIHMSID: NIHMS57970 PubMed [journal] PMID: 18538366, PMCID: PMC2504324
  • La Rosa C, Krishnan A, Longmate J, Martinez J, Manchanda P, Lacey SF, Limaye AP, Diamond DJ. Programmed death-1 expression in liver transplant recipients as a prognostic indicator of cytomegalovirus disease. The Journal of infectious diseases. 2008; 197(1):25-33. PubMed [journal] PMID: 18171281
  • La Rosa C, Limaye AP, Krishnan A, Longmate J, Diamond DJ. Longitudinal assessment of cytomegalovirus (CMV)-specific immune responses in liver transplant recipients at high risk for late CMV disease. The Journal of infectious diseases. 2007; 195(5):633-44. PubMed [journal] PMID: 17262704
  • Wang Z, La Rosa C, Li Z, Ly H, Krishnan A, Martinez J, Britt WJ, Diamond DJ. Vaccine properties of a novel marker gene-free recombinant modified vaccinia Ankara expressing immunodominant CMV antigens pp65 and IE1. Vaccine. 2007; 25(6):1132-41. NIHMSID: NIHMS16920 PubMed [journal] PMID: 17049414, PMCID: PMC1852509
  • Lacey SF, La Rosa C, Zhou W, Sharma MC, Martinez J, Krishnan A, Gallez-Hawkins G, Thao L, Longmate J, Spielberger R, Forman SJ, Limaye A, Zaia JA, Diamond DJ. Functional comparison of T cells recognizing cytomegalovirus pp65 and intermediate-early antigen polypeptides in hematopoietic stem-cell transplant and solid organ transplant recipients. The Journal of infectious diseases. 2006; 194(10):1410-21. PubMed [journal] PMID: 17054071
  • La Rosa C, Wang Z, Lacey SF, Lalimarmo MM, Krishnan A, Longmate J, Diamond DJ. In vitro expansion of polyclonal T-cell subsets for adoptive immunotherapy by recombinant modified vaccinia Ankara. Experimental hematology. 2006; 34(4):497-507. PubMed [journal] PMID: 16569596
  • Wang Z, La Rosa C, Lacey SF, Maas R, Mekhoubad S, Britt WJ, Diamond DJ. Attenuated poxvirus expressing three immunodominant CMV antigens as a vaccine strategy for CMV infection. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2006; 35(3):324-31. PubMed [journal] PMID: 16388983
  • Villacres MC, Literat O, Degiacomo M, Du W, La Rosa C, Diamond DJ, Kovacs A. Reduced type 1 and type 2 cytokines in antiviral memory T helper function among women coinfected with HIV and HCV. Journal of clinical immunology. 2005; 25(2):134-41. NIHMSID: NIHMS299896 PubMed [journal] PMID: 15821890, PMCID: PMC3127261
  • La Rosa C, Wang Z, Lacey SF, Markel SF, Sharma MC, Martinez J, Lalimarmo MM, Diamond DJ. Characterization of host immunity to cytomegalovirus pp150 (UL32). Human immunology. 2005; 66(2):116-26. PubMed [journal] PMID: 15694996
  • Wang Z, La Rosa C, Mekhoubad S, Lacey SF, Villacres MC, Markel S, Longmate J, Ellenhorn JD, Siliciano RF, Buck C, Britt WJ, Diamond DJ. Attenuated poxviruses generate clinically relevant frequencies of CMV-specific T cells. Blood. 2004; 104(3):847-56. PubMed [journal] PMID: 15090456
  • Wang Z, La Rosa C, Maas R, Ly H, Brewer J, Mekhoubad S, Daftarian P, Longmate J, Britt WJ, Diamond DJ. Recombinant modified vaccinia virus Ankara expressing a soluble form of glycoprotein B causes durable immunity and neutralizing antibodies against multiple strains of human cytomegalovirus. Journal of virology. 2004; 78(8):3965-76. PubMed [journal] PMID: 15047812, PMCID: PMC374285
  • Daftarian P, Ali S, Sharan R, Lacey SF, La Rosa C, Longmate J, Buck C, Siliciano RF, Diamond DJ. Immunization with Th-CTL fusion peptide and cytosine-phosphate-guanine DNA in transgenic HLA-A2 mice induces recognition of HIV-infected T cells and clears vaccinia virus challenge. Journal of immunology (Baltimore, Md. : 1950). 2003; 171(8):4028-39. PubMed [journal] PMID: 14530323
  • Lacey SF, Villacres MC, La Rosa C, Wang Z, Longmate J, Martinez J, Brewer JC, Mekhoubad S, Maas R, Leedom JM, Forman SJ, Zaia JA, Diamond DJ. Relative dominance of HLA-B*07 restricted CD8+ T-lymphocyte immune responses to human cytomegalovirus pp65 in persons sharing HLA-A*02 and HLA-B*07 alleles. Human immunology. 2003; 64(4):440-52. PubMed [journal] PMID: 12651070
  • La Rosa C, Wang Z, Brewer JC, Lacey SF, Villacres MC, Sharan R, Krishnan R, Crooks M, Markel S, Maas R, Diamond DJ. Preclinical development of an adjuvant-free peptide vaccine with activity against CMV pp65 in HLA transgenic mice. Blood. 2002; 100(10):3681-9. PubMed [journal] PMID: 12393676
  • Gallez-Hawkins G, Lomeli NA, L Li X, Yao ZQ, La Rosa C, Diamond DJ, Zaia JA. Kinase-deficient CMVpp65 triggers a CMVpp65 specific T-cell immune response in HLA-A*0201.Kb transgenic mice after DNA immunization. Scandinavian journal of immunology. 2002; 55(6):592-8. PubMed [journal] PMID: 12028562
  • Villacres MC, Lacey SF, La Rosa C, Krishnan R, Auge C, Longmate J, Zaia JA, Leedom JM, Diamond DJ. Human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy maintain activated CD8+ T cell subsets as a strong adaptive immune response to cytomegalovirus. The Journal of infectious diseases. 2001; 184(3):256-67. PubMed [journal] PMID: 11443550
  • La Rosa C, Krishnan R, Markel S, Schneck JP, Houghten R, Pinilla C, Diamond DJ. Enhanced immune activity of cytotoxic T-lymphocyte epitope analogs derived from positional scanning synthetic combinatorial libraries. Blood. 2001; 97(6):1776-86. PubMed [journal] PMID: 11238120
  • Zaia JA, Gallez-Hawkins G, Li X, Yao ZQ, Lomeli N, Molinder K, La Rosa C, Diamond DJ. Infrequent occurrence of natural mutations in the pp65(495-503) epitope sequence presented by the HLA A*0201 allele among human cytomegalovirus isolates. Journal of virology. 2001; 75(5):2472-4. PubMed [journal] PMID: 11160752, PMCID: PMC114832
  • Longmate J, York J, La Rosa C, Krishnan R, Zhang M, Senitzer D, Diamond DJ. Population coverage by HLA class-I restricted cytotoxic T-lymphocyte epitopes. Immunogenetics. 2001; 52(3-4):165-73. PubMed [journal] PMID: 11220618
  • Zaia JA, Sissons JG, Riddell S, Diamond DJ, Wills MR, Carmichael AJ, Weekes MP, Gandhi M, La Rosa C, Villacres M, Lacey S, Markel S, Sun J. Status of Cytomegalovirus Prevention and Treatment in 2000. Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program. 2000; :339-355. PubMed [journal] PMID: 11701550
  • Massi C, Indino E, Lami C, Fissi A, Pieroni O, La Rosa C, Esposito F, Galoppini C, Rovero P, Bandecchi P, Bendinelli M, Garzelli C. The antiviral activity of a synthetic peptide derived from the envelope SU glycoprotein of feline immunodeficiency virus maps in correspondence of an amphipathic helical segment. Biochemical and biophysical research communications. 1998; 246(1):160-5. PubMed [journal] PMID: 9600086
  • Massi C, Lombardi S, Indino E, Matteucci D, La Rosa C, Esposito F, Garzelli C, Bendinelli M. Most potential linear B cell epitopes of Env glycoproteins of feline immunodeficiency virus are immunogenically silent in infected cats. AIDS research and human retroviruses. 1997; 13(13):1121-9. PubMed [journal] PMID: 9282817
  • Lombardi S, Massi C, Indino E, La Rosa C, Mazzetti P, Falcone ML, Rovero P, Fissi A, Pieroni O, Bandecchi P, Esposito F, Tozzini F, Bendinelli M, Garzelli C. Inhibition of feline immunodeficiency virus infection in vitro by envelope glycoprotein synthetic peptides. Virology. 1996; 220(2):274-84. PubMed [journal] PMID: 8661378
  • Lombardi S, Massi C, Tozzini F, Zaccaro L, Bazzichi A, Bandecchi P, La Rosa C, Bendinelli M, Garzelli C. Epitope mapping of the V3 domain of feline immunodeficiency virus envelope glycoprotein by monoclonal antibodies. The Journal of general virology. 1995; 76 ( Pt 8):1893-9. PubMed [journal] PMID: 7636470
  • Lombardi S, Garzelli C, La Rosa C, Zaccaro L, Specter S, Malvaldi G, Tozzini F, Esposito F, Bendinelli M. Identification of a linear neutralization site within the third variable region of the feline immunodeficiency virus envelope. Journal of virology. 1993; 67(8):4742-9. PubMed [journal] PMID: 8392611, PMCID: PMC237860
  • Esposito F, Lombardi S, Modiano D, Habluetzel A, Del Nero L, Lamizana L, Pietra V, Rotigliano G, Corradin G, Ravot E. In vitro immune recognition of synthetic peptides from the Plasmodium falciparum CS protein by individuals naturally exposed to different sporozoite challenge. Immunology letters. 1992; 33(2):187-99. PubMed [journal] PMID: 1446925

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  • 1998, American Soc. of Hematol. Award to participate to the 40th ASH Conference
  • 1992, University of Camerino (Italy) award for research activity to be performed in specialized EC Institutions
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