Jay A. Berzofsky

Unsung Hero Robert C. Gallo (2009)

Abbadessa, Giovanni, Accolla, Roberto, Aiuti, Fernando, Albini, Adriana, Aldovini, Anna, Alfano, Massimo, ...

Awarding the Nobel prize in physiology or medicine to Francoise Barré-Sinoussi and Luc Montagnier for the discovery of HIV-1, the causative agent of AIDS, is timely given the harm that the virus...

Estimation of low frequency antigen-presenting cells with a novel RELISPOT assay (2008)

Dzutsev, Amiran K., Belyakov, Igor M., Isakov, Dmitry V., Gagnon, Susan J., Margulies, David H., Berzofsky, Jay A.

Adequate presentation of self and foreign antigens is a key factor for efficient T-cell immunosurveillance against pathogens and tumors. Cells presenting foreign antigens usually comprise a rare...

Avidity of CD8 T cells sharpens immunodominance (2007)

Dzutsev, Amiran H., Belyakov, Igor M., Isakov, Dmitry V., Margulies, David H., Berzofsky, Jay A.

In the course of viral infection, the immune system exploits only a fraction of the available CTL repertoire and focuses on a few of a myriad of potentially antigenic peptides. This phenomenon, known...

Avidity of CD8 T cells sharpens immunodominance (2007)

Dzutsev, Amiran H., Belyakov, Igor M., Isakov, Dmitry V., Margulies, David H., Berzofsky, Jay A.

In the course of viral infection, the immune system exploits only a fraction of the available CTL repertoire and focuses on a few of a myriad of potentially antigenic peptides. This phenomenon, known...

Avidity of CD8 T cells sharpens immunodominance (2007)

Dzutsev, Amiran H., Belyakov, Igor M., Isakov, Dmitry V., Margulies, David H., Berzofsky, Jay A.

In the course of viral infection, the immune system exploits only a fraction of the available CTL repertoire and focuses on a few of a myriad of potentially antigenic peptides. This phenomenon, known...

HPV-16 L1 VLP vaccine elicits a broad-spectrum of cytokine responses in whole blood (2005)

Pinto, Ligia A., Castle, Philip E., Roden, Richard B., Harro, Clayton D., Lowy, Douglas R., Schiller, John T., ...

Here, we evaluated innate and adaptive immune system cytokine responses induced by HPV-16 L1 VLP in whole blood (WB) cultures from individuals receiving the vaccine (n = 20) or placebo (n = 4) before...

HPV-16 L1 VLP vaccine elicits a broad-spectrum of cytokine responses in whole blood (2005)

Pinto, Ligia A., Castle, Philip E., Roden, Richard B., Harro, Clayton D., Lowy, Douglas R., Schiller, John T., ...

Here, we evaluated innate and adaptive immune system cytokine responses induced by HPV-16 L1 VLP in whole blood (WB) cultures from individuals receiving the vaccine (n = 20) or placebo (n = 4) before...

Prediction and Testing of Antigenic Sites of the Aids Virus HTLV-III, Recognized by T-Lymphocytes for the Development of Possible Synthetic Vaccine (2003)

Berzofsky, Jay A.

Whether the immune protective mechanisms against AIDS involve antibodies or cytotoxic T lymphocytes (CTL) or both, helper T cells will be necessary to induce either type of response. Also, it is...

Signals delivered through TCR instruct IL-12 receptor (IL-12R) expression: IL-12 and tumor necrosis factor-{alpha} synergize for IL-12R expression at low antigen dose (2001)

Ahlers, Jeffrey D., Belyakov, Igor M., Matsui, So, Berzofsky, Jay A.

Regulation of the IL-12 receptor (IL-12R) β2 chain has been suggested to function as a molecular switch in determining T cell phenotype. However, because most studies have been carried out under...

Counter-regulation of cytolytic activity and cytokine production in HIV-1-specific murine CD8+ cytotoxic T lymphocytes by free antigenic peptide (2001)

Takahashi, Megumi, Nakagawa, Yohko, Berzofsky, Jay A., Takahashi, Hidemi

We have reported previously that the cytolytic activity of murine CD8+ cytotoxic T lymphocytes (CTL) specific for HIV-1 gp160 envelope glycoprotein was markedly inhibited by brief exposure to...

Mechanisms of cytokine synergy essential for vaccine protection against viral challenge (2001)

Ahlers, Jeffrey D., Belyakov, Igor M., Matsui, So, Berzofsky, Jay A.

The ability of cytokines to steer CD4+ Th cell responses toward a Th1 or Th2 phenotype and enhance the magnitude of both CD8+ cytotoxic T lymphocytes (CTL) and antibody responses has...

Two intermediate-avidity cytotoxic T lymphocyte clones with a disparity between functional avidity and MHC tetramer staining (2001)

Derby, Michael A., Wang, Jian, Margulies, David H., Berzofsky, Jay A.

The efficacy of cytotoxic T lymphocytes (CTL) has been shown to be highly dependent upon their functional avidity (the sensitivity of their cellular response to MHC–peptide complexes). To examine...

Molecular Alterations in Pediatric Sarcomas: Potential Targets for Immunotherapy (1998)

Theresa J. Goletz, Crystal L. Mackall, Jay A. Berzofsky, Lee J. Helman

Purpose/results/discussion. Recurrent chromosomal translocations are common features of many human malignancies. While such translocations often serve as diagnostic markers, molecular analysis of...

Molecular analysis of presentation by HLA-A2.1 of a promiscuously binding V3 loop peptide from the HIV-1 envelope protein to human cytotoxic T lymphocytes (1996)

Alexander-Miller, Martha A., Parker, Kenneth C., Tsukui, Taku, Pendleton, C. David, Coligan, John E., Berzofsky, Jay A.

P18IIIB is a highly immunogenic peptide from the V3 loop of the HIV-1 gp160 envelope protein that is presented promiscuously by multiple class I MHC molecules. Understanding the molecular basis for...

Induction of CD8+ cytotoxic T lymphocytes by immunization with syngeneic irradiated HIV-1 envelope derived peptide-pulsed dendritic cells (1993)

Takahashi, Hidemi, Nakagawa, Yohko, Yokomuro, Kozo, Berzofsky, Jay A., Wigzell, H.

Based on the evidence that CD8+; cytotoxic T cells (CTL) precursors do not appear to distinguish between virus-infected cells and viral peptide-puised syngeneic cells, we have developed methods...

Role of conserved regions of class I MHC molecules in the activation of CD8+ cytotoxic T lymphocytes by peptide and purified cell-free class I molecules (1993)

Takeshita, Toshiyuki, Kozlowski, Steven, England, Richard D., Brower, Richard, Schneck, Jonathan, Takahashi, Hidemi, ...

To analyze the molecular interactions involved in CD8+ cytotoxic T lymphocyte (CTL) recognition quantitatively, we developed a cell-free antigen presenting system. Genetically engineered soluble...

The nature of the immune response (Ir) gene defect for pigeon cytochrome c in [B10.A(4R) x B10.PL]F1 mice: A Comparison Between Thymic Selection and Antigen Presentation (1989)

Kovac, Zdenko, Schwartz, Ronald H., Berzofsky, Jay A.

[B10.A(4R) × B10.PL]F1 mice are low responders to pigeon cytochrome c, while [B10.A(2R) × B10.PL]F1 and B10.A mice are high responders. The in vivo site at which the different aliomorphs of the Ea...

Mucosal vaccination overcomes the barrier to recombinant vaccinia immunization caused by preexisting poxvirus immunity

Belyakov, Igor M., Moss, Bernard, Strober, Warren, Berzofsky, Jay A.

Overcoming preexisting immunity to vaccinia virus in the adult population is a key requirement for development of otherwise potent recombinant vaccinia vaccines. Based on our observation that s.c....

Mucosal immunization with HIV-1 peptide vaccine induces mucosal and systemic cytotoxic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge

Belyakov, Igor M., Derby, Michael A., Ahlers, Jeffrey D., Kelsall, Brian L., Earl, Patricia, Moss, Bernard, ...

Mucosal tissues are major sites of HIV entry and initial infection. Thus, the induction of a mucosal cytotoxic T lymphocyte (CTL) response is an important feature for an effective HIV vaccine....

Enhanced immunogenicity of HIV-1 vaccine construct by modification of the native peptide sequence

Ahlers, Jeffrey D., Takeshita, Toshiyuki, Pendleton, C. David, Berzofsky, Jay A.

Viral proteins are not naturally selected for high affinity major histocompatibility complex (MHC) binding sequences; indeed, if there is any selection, it is likely to be negative in nature. Thus,...

Targeting HIV proteins to the major histocompatibility complex class I processing pathway with a novel gp120-anthrax toxin fusion protein

Goletz, Theresa J., Klimpel, Kurt R., Arora, Naveen, Leppla, Stephen H., Keith, Jerry M., Berzofsky, Jay A.

A challenge for subunit vaccines whose goal is to elicit CD8+ cytotoxic T lymphocytes (CTLs) is to deliver the antigen to the cytosol of the living cell, where it can be processed for presentation by...

Prophylactic DNA vaccine for hepatitis C virus (HCV) infection: HCV-specific cytotoxic T lymphocyte induction and protection from HCV-recombinant vaccinia infection in an HLA-A2.1 transgenic mouse model

Arichi, Tatsumi, Saito, Takafumi, Major, Marian E., Belyakov, Igor M., Shirai, Mutsunori, Engelhard, Victor H., ...

DNA vaccines express antigens intracellularly and effectively induce cellular immune responses. Because only chimpanzees can be used to model human hepatitis C virus (HCV) infections, we developed a...

Characterization of Conserved T- and B-Cell Epitopes in Plasmodium falciparum Major Merozoite Surface Protein 1

Parra, Marcela, Hui, George, Johnson, Armead H., Berzofsky, Jay A., Roberts, Theodore, Quakyi, Isabella A., ...

Vaccines for P. falciparum will need to contain both T- and B-cell epitopes. Conserved epitopes are the most desirable, but they are often poorly immunogenic. The major merozoite surface protein 1...

Induction of a Mucosal Cytotoxic T-Lymphocyte Response by Intrarectal Immunization with a Replication-Deficient Recombinant Vaccinia Virus Expressing Human Immunodeficiency Virus 89.6 Envelope Protein

Belyakov, Igor M., Wyatt, Linda S., Ahlers, Jeffrey D., Earl, Patricia, Pendleton, C. David, Kelsall, Brian L., ...

To improve the safety of recombinant vaccinia virus vaccines, modified vaccinia virus Ankara (MVA) has been employed, because it has a replication defect in most mammalian cells. Here we apply MVA to...

Impairment of Gag-Specific CD8+ T-Cell Function in Mucosal and Systemic Compartments of Simian Immunodeficiency Virus mac251- and Simian-Human Immunodeficiency Virus KU2-Infected Macaques

Hel, Zdenek, Nacsa, Janos, Kelsall, Brian, Tsai, Wen-Po, Letvin, Norman, Parks, Robyn Washington, ...

The identification of several simian immunodeficiency virus mac251 (SIVmac251) cytotoxic T-lymphocyte epitopes recognized by CD8+ T cells of infected rhesus macaques carrying the Mamu-A*01 molecule...

Granulocyte-Macrophage Colony-Stimulating Factor Expressed by Recombinant Respiratory Syncytial Virus Attenuates Viral Replication and Increases the Level of Pulmonary Antigen-Presenting Cells

Bukreyev, Alexander, Belyakov, Igor M., Berzofsky, Jay A., Murphy, Brian R., Collins, Peter L.

An obstacle to developing a vaccine against human respiratory syncytial virus (RSV) is that natural infection typically does not confer solid immunity to reinfection. To investigate methods to...

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

Ahlers, Jeffrey D., Belyakov, Igor M., Terabe, Masaki, Koka, Rima, Donaldson, Debra D., Thomas, Elaine K., ...

Although a role for CD4+ helper cells in CD8+ cytotoxic T lymphocyte (CTL) induction by vaccines is widely recognized, much less is known about a counterbalancing role of CD4+ T cells in...

Effects of Cytotoxic T Lymphocytes (CTL) Directed against a Single Simian Immunodeficiency Virus (SIV) Gag CTL Epitope on the Course of SIVmac239 Infection

Allen, Todd M., Jing, Peicheng, Calore, Briana, Horton, Helen, O'Connor, David H., Hanke, Tomas, ...

Vaccine-induced cytotoxic T lymphocytes (CTL) have been implicated in the control of virus replication in simian immunodeficiency virus (SIV)-challenged and simian-human immunodeficiency...

Coadministration of HIV vaccine vectors with vaccinia viruses expressing IL-15 but not IL-2 induces long-lasting cellular immunity

Oh, SangKon, Berzofsky, Jay A., Burke, Donald S., Waldmann, Thomas A., Perera, Liyanage P.

Vaccine efficacy is determined largely by cellular and humoral immunity as well as long-lasting immunological memory. IL-2 and IL-15 were evaluated in vaccinia vectors expressing HIV gp160 for the...

Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses

Belyakov, Igor M., Earl, Patricia, Dzutsev, Amiran, Kuznetsov, Vladimir A., Lemon, Michael, Wyatt, Linda S., ...

The concern about bioterrorism with smallpox has raised the possibility of widespread vaccination, but the greater prevalence of immunocompromised individuals today requires a safer vaccine, and the...

High-affinity T helper epitope induces complementary helper and APC polarization, increased CTL, and protection against viral infection

Ahlers, Jeffrey D., Belyakov, Igor M., Thomas, Elaine K., Berzofsky, Jay A.

Natural viral proteins do not always make optimal vaccines. We have found that sequence modification to increase epitope affinity for class II MHC molecules (epitope enhancement) can improve...

Transcutaneous immunization induces mucosal CTLs and protective immunity by migration of primed skin dendritic cells

Belyakov, Igor M., Hammond, Scott A., Ahlers, Jeffrey D., Glenn, Gregory M., Berzofsky, Jay A.

Transcutaneous immunization (TCI), the application of vaccines on the skin, induces robust systemic and mucosal antibodies in animal models and in humans. The means by which mucosal immune responses...

Distinct H-2-linked Ir genes control both antibody and T cell responses to different determinants on the same antigen, myoglobin*

Berzofsky, Jay A., Richman, Lee K., Killion, Douglas J.

The murine antibody and T lymphocyte proliferative responses to sperm whale myoglobin (Mb) were found to be under control of two distinct H-2-linked immune response (Ir) genes (Ir-Mb-1, mapping in...

Progress on new vaccine strategies for the immunotherapy and prevention of cancer

Berzofsky, Jay A., Terabe, Masaki, Oh, SangKon, Belyakov, Igor M., Ahlers, Jeffrey D., Janik, John E., ...

In recent years, great strides in understanding and regulating the immune system have led to new hope for harnessing its exquisite specificity to destroy cancer cells without affecting normal...

Protection against Lethal Vaccinia Virus Challenge in HLA-A2 Transgenic Mice by Immunization with a Single CD8+ T-Cell Peptide Epitope of Vaccinia and Variola Viruses

Snyder, James T., Belyakov, Igor M., Dzutsev, Amiran, Lemonnier, François, Berzofsky, Jay A.

CD8+ T lymphocytes have been shown to be involved in controlling poxvirus infection, but no protective cytotoxic T-lymphocyte (CTL) epitopes are defined for variola virus, the causative agent of...

Progress on new vaccine strategies against chronic viral infections

Berzofsky, Jay A., Ahlers, Jeffrey D., Janik, John, Morris, John, Oh, SangKon, Terabe, Masaki, ...

Among the most cost-effective strategies for preventing viral infections, vaccines have proven effective primarily against viruses causing acute, self-limited infections. For these it has been...

IL-15/IL-15Rα-mediated avidity maturation of memory CD8+ T cells

Oh, SangKon, Perera, Liyanage P., Burke, Donald S., Waldmann, Thomas A., Berzofsky, Jay A.

T cell avidity is critical to viral clearance, but mechanisms of CD8+ T cell avidity maturation are poorly understood. Here, we find that IL-15 mediates two mechanisms of avidity maturation. (i) By...

Systemic Immunization with an ALVAC-HIV-1/Protein Boost Vaccine Strategy Protects Rhesus Macaques from CD4+ T-Cell Loss and Reduces both Systemic and Mucosal Simian-Human Immunodeficiency Virus SHIVKU2 RNA Levels

Pal, Ranajit, Venzon, David, Santra, Sampa, Kalyanaraman, Vaniambadi S., Montefiori, David C., Hocker, Lindsey, ...

Transmission of human immunodeficiency virus type 1 (HIV-1) occurs primarily via the mucosal route, suggesting that HIV-1 vaccines may need to elicit mucosal immune responses. Here, we investigated...

The NS2 Protein of Human Respiratory Syncytial Virus Suppresses the Cytotoxic T-Cell Response as a Consequence of Suppressing the Type I Interferon Response

Kotelkin, Alexander, Belyakov, Igor M., Yang, Lijuan, Berzofsky, Jay A., Collins, Peter L., Bukreyev, Alexander

The NS1 and NS2 proteins of human respiratory syncytial virus (HRSV) have been shown to antagonize the type I interferon (IFN) response, an effect subject to host range constraints. We have now found...

Mucosal vaccination overcomes the barrier to recombinant vaccinia immunization caused by preexisting poxvirus immunity

Belyakov, Igor M., Moss, Bernard, Strober, Warren, Berzofsky, Jay A.

Overcoming preexisting immunity to vaccinia virus in the adult population is a key requirement for development of otherwise potent recombinant vaccinia vaccines. Based on our observation that s.c....

Mucosal immunization with HIV-1 peptide vaccine induces mucosal and systemic cytotoxic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge

Belyakov, Igor M., Derby, Michael A., Ahlers, Jeffrey D., Kelsall, Brian L., Earl, Patricia, Moss, Bernard, ...

Mucosal tissues are major sites of HIV entry and initial infection. Thus, the induction of a mucosal cytotoxic T lymphocyte (CTL) response is an important feature for an effective HIV vaccine....

Enhanced immunogenicity of HIV-1 vaccine construct by modification of the native peptide sequence

Ahlers, Jeffrey D., Takeshita, Toshiyuki, Pendleton, C. David, Berzofsky, Jay A.

Viral proteins are not naturally selected for high affinity major histocompatibility complex (MHC) binding sequences; indeed, if there is any selection, it is likely to be negative in nature. Thus,...

Targeting HIV proteins to the major histocompatibility complex class I processing pathway with a novel gp120-anthrax toxin fusion protein

Goletz, Theresa J., Klimpel, Kurt R., Arora, Naveen, Leppla, Stephen H., Keith, Jerry M., Berzofsky, Jay A.

A challenge for subunit vaccines whose goal is to elicit CD8+ cytotoxic T lymphocytes (CTLs) is to deliver the antigen to the cytosol of the living cell, where it can be processed for presentation by...

Prophylactic DNA vaccine for hepatitis C virus (HCV) infection: HCV-specific cytotoxic T lymphocyte induction and protection from HCV-recombinant vaccinia infection in an HLA-A2.1 transgenic mouse model

Arichi, Tatsumi, Saito, Takafumi, Major, Marian E., Belyakov, Igor M., Shirai, Mutsunori, Engelhard, Victor H., ...

DNA vaccines express antigens intracellularly and effectively induce cellular immune responses. Because only chimpanzees can be used to model human hepatitis C virus (HCV) infections, we developed a...

Characterization of Conserved T- and B-Cell Epitopes in Plasmodium falciparum Major Merozoite Surface Protein 1

Parra, Marcela, Hui, George, Johnson, Armead H., Berzofsky, Jay A., Roberts, Theodore, Quakyi, Isabella A., ...

Vaccines for P. falciparum will need to contain both T- and B-cell epitopes. Conserved epitopes are the most desirable, but they are often poorly immunogenic. The major merozoite surface protein 1...

Induction of a Mucosal Cytotoxic T-Lymphocyte Response by Intrarectal Immunization with a Replication-Deficient Recombinant Vaccinia Virus Expressing Human Immunodeficiency Virus 89.6 Envelope Protein

Belyakov, Igor M., Wyatt, Linda S., Ahlers, Jeffrey D., Earl, Patricia, Pendleton, C. David, Kelsall, Brian L., ...

To improve the safety of recombinant vaccinia virus vaccines, modified vaccinia virus Ankara (MVA) has been employed, because it has a replication defect in most mammalian cells. Here we apply MVA to...

Impairment of Gag-Specific CD8+ T-Cell Function in Mucosal and Systemic Compartments of Simian Immunodeficiency Virus mac251- and Simian-Human Immunodeficiency Virus KU2-Infected Macaques

Hel, Zdenek, Nacsa, Janos, Kelsall, Brian, Tsai, Wen-Po, Letvin, Norman, Parks, Robyn Washington, ...

The identification of several simian immunodeficiency virus mac251 (SIVmac251) cytotoxic T-lymphocyte epitopes recognized by CD8+ T cells of infected rhesus macaques carrying the Mamu-A*01 molecule...

Granulocyte-Macrophage Colony-Stimulating Factor Expressed by Recombinant Respiratory Syncytial Virus Attenuates Viral Replication and Increases the Level of Pulmonary Antigen-Presenting Cells

Bukreyev, Alexander, Belyakov, Igor M., Berzofsky, Jay A., Murphy, Brian R., Collins, Peter L.

An obstacle to developing a vaccine against human respiratory syncytial virus (RSV) is that natural infection typically does not confer solid immunity to reinfection. To investigate methods to...

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

Ahlers, Jeffrey D., Belyakov, Igor M., Terabe, Masaki, Koka, Rima, Donaldson, Debra D., Thomas, Elaine K., ...

Although a role for CD4+ helper cells in CD8+ cytotoxic T lymphocyte (CTL) induction by vaccines is widely recognized, much less is known about a counterbalancing role of CD4+ T cells in...

Effects of Cytotoxic T Lymphocytes (CTL) Directed against a Single Simian Immunodeficiency Virus (SIV) Gag CTL Epitope on the Course of SIVmac239 Infection

Allen, Todd M., Jing, Peicheng, Calore, Briana, Horton, Helen, O'Connor, David H., Hanke, Tomas, ...

Vaccine-induced cytotoxic T lymphocytes (CTL) have been implicated in the control of virus replication in simian immunodeficiency virus (SIV)-challenged and simian-human immunodeficiency...

Coadministration of HIV vaccine vectors with vaccinia viruses expressing IL-15 but not IL-2 induces long-lasting cellular immunity

Oh, SangKon, Berzofsky, Jay A., Burke, Donald S., Waldmann, Thomas A., Perera, Liyanage P.

Vaccine efficacy is determined largely by cellular and humoral immunity as well as long-lasting immunological memory. IL-2 and IL-15 were evaluated in vaccinia vectors expressing HIV gp160 for the...

Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses

Belyakov, Igor M., Earl, Patricia, Dzutsev, Amiran, Kuznetsov, Vladimir A., Lemon, Michael, Wyatt, Linda S., ...

The concern about bioterrorism with smallpox has raised the possibility of widespread vaccination, but the greater prevalence of immunocompromised individuals today requires a safer vaccine, and the...

High-affinity T helper epitope induces complementary helper and APC polarization, increased CTL, and protection against viral infection

Ahlers, Jeffrey D., Belyakov, Igor M., Thomas, Elaine K., Berzofsky, Jay A.

Natural viral proteins do not always make optimal vaccines. We have found that sequence modification to increase epitope affinity for class II MHC molecules (epitope enhancement) can improve...

Transcutaneous immunization induces mucosal CTLs and protective immunity by migration of primed skin dendritic cells

Belyakov, Igor M., Hammond, Scott A., Ahlers, Jeffrey D., Glenn, Gregory M., Berzofsky, Jay A.

Transcutaneous immunization (TCI), the application of vaccines on the skin, induces robust systemic and mucosal antibodies in animal models and in humans. The means by which mucosal immune responses...

Distinct H-2-linked Ir genes control both antibody and T cell responses to different determinants on the same antigen, myoglobin*

Berzofsky, Jay A., Richman, Lee K., Killion, Douglas J.

The murine antibody and T lymphocyte proliferative responses to sperm whale myoglobin (Mb) were found to be under control of two distinct H-2-linked immune response (Ir) genes (Ir-Mb-1, mapping in...

Progress on new vaccine strategies for the immunotherapy and prevention of cancer

Berzofsky, Jay A., Terabe, Masaki, Oh, SangKon, Belyakov, Igor M., Ahlers, Jeffrey D., Janik, John E., ...

In recent years, great strides in understanding and regulating the immune system have led to new hope for harnessing its exquisite specificity to destroy cancer cells without affecting normal...

Protection against Lethal Vaccinia Virus Challenge in HLA-A2 Transgenic Mice by Immunization with a Single CD8+ T-Cell Peptide Epitope of Vaccinia and Variola Viruses

Snyder, James T., Belyakov, Igor M., Dzutsev, Amiran, Lemonnier, François, Berzofsky, Jay A.

CD8+ T lymphocytes have been shown to be involved in controlling poxvirus infection, but no protective cytotoxic T-lymphocyte (CTL) epitopes are defined for variola virus, the causative agent of...

Progress on new vaccine strategies against chronic viral infections

Berzofsky, Jay A., Ahlers, Jeffrey D., Janik, John, Morris, John, Oh, SangKon, Terabe, Masaki, ...

Among the most cost-effective strategies for preventing viral infections, vaccines have proven effective primarily against viruses causing acute, self-limited infections. For these it has been...

IL-15/IL-15Rα-mediated avidity maturation of memory CD8+ T cells

Oh, SangKon, Perera, Liyanage P., Burke, Donald S., Waldmann, Thomas A., Berzofsky, Jay A.

T cell avidity is critical to viral clearance, but mechanisms of CD8+ T cell avidity maturation are poorly understood. Here, we find that IL-15 mediates two mechanisms of avidity maturation. (i) By...

Systemic Immunization with an ALVAC-HIV-1/Protein Boost Vaccine Strategy Protects Rhesus Macaques from CD4+ T-Cell Loss and Reduces both Systemic and Mucosal Simian-Human Immunodeficiency Virus SHIVKU2 RNA Levels

Pal, Ranajit, Venzon, David, Santra, Sampa, Kalyanaraman, Vaniambadi S., Montefiori, David C., Hocker, Lindsey, ...

Transmission of human immunodeficiency virus type 1 (HIV-1) occurs primarily via the mucosal route, suggesting that HIV-1 vaccines may need to elicit mucosal immune responses. Here, we investigated...

The NS2 Protein of Human Respiratory Syncytial Virus Suppresses the Cytotoxic T-Cell Response as a Consequence of Suppressing the Type I Interferon Response

Kotelkin, Alexander, Belyakov, Igor M., Yang, Lijuan, Berzofsky, Jay A., Collins, Peter L., Bukreyev, Alexander

The NS1 and NS2 proteins of human respiratory syncytial virus (HRSV) have been shown to antagonize the type I interferon (IFN) response, an effect subject to host range constraints. We have now found...

Possible Therapeutic Vaccine Strategy against Human Immunodeficiency Virus Escape from Reverse Transcriptase Inhibitors Studied in HLA-A2 Transgenic Mice▿

Okazaki, Takahiro, Terabe, Masaki, Catanzaro, Andrew T., Pendleton, C. David, Yarchoan, Robert, Berzofsky, Jay A.

Mutation of human immunodeficiency virus (HIV) leading to escape from anti-HIV drugs is the greatest challenge to the treatment of HIV infection. High-grade resistance to the nucleoside reverse...

Impact of vaccine-induced mucosal high-avidity CD8+CTLs in delay of AIDS viral dissemination from mucosa

Belyakov, Igor M., Kuznetsov, Vladimir A., Kelsall, Brian, Klinman, Dennis, Moniuszko, Marcin, Lemon, Michael, ...

Natural HIV transmission occurs through mucosa, but it is debated whether mucosal cytotoxic T lymphocytes (CTLs) can prevent or reduce dissemination from the initial mucosal site to the systemic...

Development of Smallpox Vaccine Candidates with Integrated Interleukin-15 That Demonstrate Superior Immunogenicity, Efficacy, and Safety in Mice▿

Perera, Liyanage P., Waldmann, Thomas A., Mosca, Joseph D., Baldwin, Nicole, Berzofsky, Jay A., Oh, Sang-Kon

The potential use of variola virus, the etiological agent of smallpox, as a bioterror agent has heightened the interest in the reinitiation of smallpox vaccination. However, the currently licensed...

Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function

Zeng, Rong, Spolski, Rosanne, Finkelstein, Steven E., Oh, SangKon, Kovanen, Panu E., Hinrichs, Christian S., ...

Interleukin (IL)-21 is the most recently recognized of the cytokines that share the common cytokine receptor γ chain (γc), which is mutated in humans with X-linked severe combined immunodeficiency....

A nonclassical non-Vα14Jα18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance

Terabe, Masaki, Swann, Jeremy, Ambrosino, Elena, Sinha, Pratima, Takaku, Shun, Hayakawa, Yoshihiro, ...

The importance of immunoregulatory T cells has become increasingly apparent. Both CD4+CD25+ T cells and CD1d-restricted NKT cells have been reported to down-regulate tumor immunity in mouse tumor...

Transforming Growth Factor-β Production and Myeloid Cells Are an Effector Mechanism through Which CD1d-restricted T Cells Block Cytotoxic T Lymphocyte–mediated Tumor Immunosurveillance: Abrogation Prevents Tumor Recurrence

Terabe, Masaki, Matsui, So, Park, Jong-Myun, Mamura, Mizuko, Noben-Trauth, Nancy, Donaldson, Debra D., ...

Our previous work demonstrated that cytotoxic T lymphocyte (CTL)-mediated tumor immunosurveillance of the 15-12RM tumor could be suppressed by a CD1d-restricted lymphocyte, most likely a natural...

Supraoptimal Peptide–Major Histocompatibility Complex Causes a Decrease in Bcl-2 Levels and Allows Tumor Necrosis Factor α Receptor II–mediated Apoptosis of Cytotoxic T Lymphocytes

Alexander-Miller, Martha A., Derby, Michael A., Sarin, Apurva, Henkart, Pierre A., Berzofsky, Jay A.

Cytotoxic T lymphocytes (CTLs) are primary mediators of viral clearance, but high viral burden can result in deletion of antigen-specific CTLs. We previously reported a potential mechanism for this...

Molecular Alterations in Pediatric Sarcomas: Potential Targets for Immunotherapy

Goletz, Theresa J., Mackall, Crystal L., Berzofsky, Jay A., Helman, Lee J.

Purpose/results/discussion. Recurrent chromosomal translocations are common features of many human malignancies. While such translocations often serve as diagnostic markers, molecular analysis of...

IL-15 as a mediator of CD4+ help for CD8+ T cell longevity and avoidance of TRAIL-mediated apoptosis

Oh, SangKon, Perera, Liyanage P., Terabe, Masaki, Ni, Ling, Waldmann, Thomas A., Berzofsky, Jay A.

CD4+ helper T cells contribute to the induction and maintenance of antigen-specific CD8+ T cells. Their absence results in short-lived antigen-specific CD8+ T cells and defective secondary CD8+ T...

Toll-like receptor ligands synergize through distinct dendritic cell pathways to induce T cell responses: Implications for vaccines

Zhu, Qing, Egelston, Colt, Vivekanandhan, Aravindhan, Uematsu, Satoshi, Akira, Shizuo, Klinman, Dennis M., ...

Toll-like receptors (TLRs) may need to cooperate with each other to be effective in detecting imminent infection and trigger immune responses. Understanding is still limited about the intracellular...

Pathogenic Roles of CD14, Galectin-3, and OX40 during Experimental Cerebral Malaria in Mice

Oakley, Miranda S., Majam, Victoria, Mahajan, Babita, Gerald, Noel, Anantharaman, Vivek, Ward, Jerrold M., ...

An in-depth knowledge of the host molecules and biological pathways that contribute towards the pathogenesis of cerebral malaria would help guide the development of novel prognostics and...