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607 results on '"Melief, Cornelis J. M."'

2. A third vaccination with a single T cell epitope confers protection in a murine model of SARS-CoV-2 infection

Author

Pardieck, Iris N., van der Sluis, Tetje C., van der Gracht, Esmé T. I., Veerkamp, Dominique M. B., Behr, Felix M., van Duikeren, Suzanne, Beyrend, Guillaume, Rip, Jasper, Nadafi, Reza, Beyranvand Nejad, Elham, Mülling, Nils, Brasem, Dena J., Camps, Marcel G. M., Myeni, Sebenzile K., Bredenbeek, Peter J., Kikkert, Marjolein, Kim, Yeonsu, Cicin-Sain, Luka, Abdelaal, Tamim, van Gisbergen, Klaas P. J. M., Franken, Kees L. M. C., Drijfhout, Jan Wouter, Melief, Cornelis J. M., Zondag, Gerben C. M., Ossendorp, Ferry, and Arens, Ramon

Published
2022
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5. Delayed vaccine-induced CD8+T cell expansion by topoisomerase I inhibition mediates enhanced CD70-dependent tumor eradication

Author

van der Sluis, Tetje C, primary, van Haften, Floortje J, additional, van Duikeren, Suzanne, additional, Pardieck, Iris N, additional, de Graaf, J Fréderique, additional, Vleeshouwers, Ward, additional, van der Maaden, Koen, additional, Melief, Cornelis J M, additional, van der Burg, Sjoerd H, additional, and Arens, Ramon, additional

Published
2023
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6. Induction of broad multifunctional CD8+ and CD4+ T cells by hepatitis B virus antigen-based synthetic long peptides ex vivo

Author

Jansen, Diahann T. S. L., primary, de Beijer, Monique T. A., additional, Luijten, Robbie J., additional, Kwappenberg, Kitty, additional, Wiekmeijer, Anna-Sophia, additional, Kessler, Amy L., additional, Pieterman, Roel F. A., additional, Bouzid, Rachid, additional, Krebber, Willem-Jan, additional, de Man, Robert A., additional, Melief, Cornelis J. M., additional, and Buschow, Sonja I., additional

Published
2023
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13. Intradermal vaccination of HPV-16 E6 synthetic peptides conjugated to an optimized Toll-like receptor 2 ligand shows safety and potent T cell immunogenicity in patients with HPV-16 positive (pre-)malignant lesions

Author

Speetjens, Frank M, primary, Welters, Marij J P, additional, Slingerland, Marije, additional, van Poelgeest, Mariette I E, additional, de Vos van Steenwijk, Peggy J, additional, Roozen, Inge, additional, Boekestijn, Sanne, additional, Loof, Nikki M, additional, Zom, Gijs G, additional, Valentijn, A Rob P M, additional, Krebber, Willem-Jan, additional, Meeuwenoord, Nico J, additional, Janssen, Catharina A H, additional, Melief, Cornelis J M, additional, van der Marel, Gijs A, additional, Filippov, Dmitri V, additional, van der Burg, Sjoerd H, additional, Gelderblom, Hans, additional, and Ossendorp, Ferry, additional

Published
2022
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15. Enhanced HPV16 E6/E7+ tumor eradication via induction of tumor-specific T cells by therapeutic vaccination with virosomes presenting synthetic long peptides.

Author

Stegmann, Toon, Wiekmeijer, Anna-Sophia, Kwappenberg, Kitty, van Duikeren, Suzanne, Bhoelan, Farien, Bemelman, Denzel, Beenakker, Thomas J. M., Krebber, Willem-Jan, Arens, Ramon, and Melief, Cornelis J. M.

Subjects
T cells, PEPTIDOMIMETICS, T cell receptors, CANCER vaccines, HUMAN papillomavirus, PEPTIDES
Abstract

Therapeutic cancer vaccines trigger CD4 + and CD8 + T cell responses capable of established tumor eradication. Current platforms include DNA, mRNA and synthetic long peptide (SLP) vaccines, all aiming at robust T cell responses. SLPs linked to the Amplivant® adjuvant (Amplivant-SLP) have shown effective delivery to dendritic cells, resulting in improved immunogenicity in mice. We have now tested virosomes as a delivery vehicle for SLPs. Virosomes are nanoparticles made from influenza virus membranes and have been used as vaccines for a variety of antigens. Amplivant-SLP virosomes induced the expansion of more antigen-specific CD8 + T memory cells in ex vivo experiments with human PBMCs than Amplivant-SLP conjugates alone. The immune response could be further improved by including the adjuvants QS-21 and 3D-PHAD in the virosomal membrane. In these experiments, the SLPs were anchored in the membrane through the hydrophobic Amplivant adjuvant. In a therapeutic mouse model of HPV16 E6/E7+ cancer, mice were vaccinated with virosomes loaded with either Amplivant-conjugated SLPs or lipid-coupled SLPs. Vaccination with both types of virosomes significantly improved the control of tumor outgrowth, leading to elimination of the tumors in about half the animals for the best combinations of adjuvants and to their survival beyond 100 days. [ABSTRACT FROM AUTHOR]

Published
2023
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16. Peptide emulsions in incomplete Freund's adjuvant create effective nurseries promoting egress of systemic CD4(+) and CD8(+) T cells for immunotherapy of cancer

Author

Melssen, Marit M., Fisher, Caroline T., Slingluff, Craig L., Melief, Cornelis J. M., Melssen, Marit M., Fisher, Caroline T., Slingluff, Craig L., and Melief, Cornelis J. M.

Abstract

Water-in-oil emulsion incomplete Freund's adjuvant (IFA) has been used as an adjuvant in preventive and therapeutic vaccines since its development. New generation, highly purified modulations of the adjuvant, Montanide incomplete seppic adjuvant (ISA)-51 and Montanide ISA-720, were developed to reduce toxicity. Montanide adjuvants are generally considered to be safe, with adverse events largely consisting of antigen and adjuvant dose-dependent injection site reactions (ISRs). Peptide vaccines in Montanide ISA-51 or ISA-720 are capable of inducing both high antibody titers and durable effector T cell responses. However, an efficient T cell response depends on the affinity of the peptide to the presenting major histocompatibility complex class I molecule, CD4(+) T cell help and/or the level of co-stimulation. In fact, in the therapeutic cancer vaccine setting, presence of a CD4(+) T cell epitope seems crucial to elicit a robust and durable systemic T cell response. Additional inclusion of a Toll-like receptor ligand can further increase the magnitude and durability of the response. Use of extended peptides that need a processing step only accomplished effectively by dendritic cells (DCs) can help to avoid antigen presentation by nucleated cells other than DC. Based on recent clinical trial results, therapeutic peptide-based cancer vaccines using emulsions in adjuvant Montanide ISA-51 can elicit robust antitumor immune responses, provided that sufficient tumor-specific CD4(+) T cell help is given in addition to CD8(+) T cell epitopes. Co-treatment with PD-1 T cell checkpoint inhibitor, chemotherapy or other immunomodulatory drugs may address local and systemic immunosuppressive mechanisms, and further enhance efficacy of therapeutic cancer peptide vaccines in IFA and its modern variants. Blinded randomized placebo-controlled trials are critical to definitively prove clinical efficacy. Mineral oil-based adjuvants for preventive vaccines, to tackle spread and severity of

Published
2022
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17. Cancer: Precision T-cell therapy targets tumours

Author

Melief, Cornelis J. M.

Subjects
Cancer treatment -- Methods, T cells -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Cornelis J. M. Melief (corresponding author) [1] A goal of treating cancer is the eradication of tumour cells while sparing healthy cells. Conventional therapeutic approaches such as chemotherapy or [...]

Published
2017
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19. Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responses

Author

Welters, Marij J. P., Kenter, Gemma G., de Vos van Steenwijk, Peggy J., Löwik, Margriet J. G., der Meer, Dorien M. A. Berends-van, Essahsah, Farah, Stynenbosch, Linda F. M., Vloon, Annelies P. G., Ramwadhdoebe, Tamara H., Piersma, Sytse J., van der Hulst, Jeanette M., Valentijn, A. Rob P. M., Fathers, Lorraine M., Drijfhout, Jan W., Franken, Kees L. M. C., Oostendorp, Jaap, Fleuren, Gert Jan, Melief, Cornelis J. M., van der Burg, Sjoerd H., and van Rood, Johannes J.

Published
2010

24. ISA101 and nivolumab for HPV-16+ cancer: updated clinical efficacy and immune correlates of response

Author

Sousa, Luana Guimaraes de, primary, Rajapakshe, Kimal, additional, Rodriguez Canales, Jaime, additional, Chin, Renee L, additional, Feng, Lei, additional, Wang, Qi, additional, Barrese, Tomas Z, additional, Massarelli, Erminia, additional, William, William, additional, Johnson, Faye M, additional, Ferrarotto, Renata, additional, Wistuba, Ignacio, additional, Coarfa, Cristian, additional, Lee, Jack, additional, Wang, Jing, additional, Melief, Cornelis J M, additional, Curran, Michael A, additional, and Glisson, Bonnie S, additional

Published
2022
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26. The long-term immune response after HPV16 peptide vaccination in women with low-grade pre-malignant disorders of the uterine cervix: a placebo-controlled phase II study

Author

de Vos van Steenwijk, Peggy J., van Poelgeest, Mariette I. E., Ramwadhdoebe, Tamara H., Löwik, Margriet J. G., Berends-van der Meer, Dorien M. A., van der Minne, Caroline E., Loof, Nikki M., Stynenbosch, Linda F. M., Fathers, Lorraine M., Valentijn, A. Rob P. M., Oostendorp, Jaap, Osse, Elisabeth M., Fleuren, Gert Jan, Nooij, Linda, Kagie, Marjolein J., Hellebrekers, Bart W. J., Melief, Cornelis J. M., Welters, Marij J. P., van der Burg, Sjoerd H., and Kenter, Gemma G.

Published
2014
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29. IFN‐γ‐induced PD‐L1 expression on human melanocytes is impaired in vitiligo

Author

Willemsen, Marcella, primary, Krebbers, Gabrielle, additional, Tjin, Esther P. M., additional, Willemsen, Karin J., additional, Louis, Alesha, additional, Konijn, Veronique A. L., additional, Narayan, Vidhya S., additional, Post, Nicoline F., additional, Bakker, Walbert J., additional, Melief, Cornelis J. M., additional, Bekkenk, Marcel W., additional, and Luiten, Rosalie M., additional

Published
2021
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31. A placebo-controlled randomized HPV16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesions

Author

de Vos van Steenwijk, Peggy J., Ramwadhdoebe, Tamara H., Löwik, Margriet J. G., van der Minne, Caroline E., Berends-van der Meer, Dorien M. A., Fathers, Lorraine M., Valentijn, A. Rob P. M., Oostendorp, Jaap, Fleuren, Gert Jan, Hellebrekers, Bart W. J., Welters, Marij J. P., van Poelgeest, Mariette I., Melief, Cornelis J. M., Kenter, Gemma G., and van der Burg, Sjoerd H.

Published
2012
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32. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens

Author

Gubin, Matthew M., Zhang, Xiuli, Schuster, Heiko, Caron, Etienne, Ward, Jeffrey P., Noguchi, Takuro, Ivanova, Yulia, Hundal, Jasreet, Arthur, Cora D., Krebber, Willem-Jan, Mulder, Gwenn E., Toebes, Mireille, Vesely, Matthew D., Lam, Samuel S. K., Korman, Alan J., Allison, James P., Freeman, Gordon J., Sharpe, Arlene H., Pearce, Erika L., Schumacher, Ton N., Aebersold, Ruedi, Rammensee, Hans-Georg, Melief, Cornelis J. M., Mardis, Elaine R., Gillanders, William E., Artyomov, Maxim N., and Schreiber, Robert D.

Published
2014
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33. Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants

Author

van Hall, Thorbald, Wolpert, Elisabeth Z, van Veelen, Peter, Laban, Sandra, van der Veer, Michael, Roseboom, Marjet, Bres, Sandra, Grufman, Per, de Ru, Arnoud, Meiring, Hugo, de Jong, Ad, Franken, Kees, Teixeira, Antoinette, Valentijn, Rob, Drijfhout, Jan Wouter, Koning, Frits, Camps, Marcel, Ossendorp, Ferry, Karre, Klas, Ljunggren, Hans-Gustaf, Melief, Cornelis J M, and Offringa, Rienk

Abstract

Defects in major histocompatibility complex (MHC) class I-restricted antigen presentation are frequently observed in human cancers and result in escape of tumors from cytotoxic T lymphocyte (CTL) immune surveillance in mice. Here, we show the existence of a unique category of CTLs that can prevent this escape. The CTLs target an alternative repertoire of peptide epitopes that emerge in MHC class I at the surface of cells with impaired function of transporter associated with antigen processing (TAP), tapasin or the proteasome. These peptides, although derived from self antigens such as the commonly expressed Lass5 protein (also known as Trh4), are not presented by normal cells. This explains why they act as immunogenic neoantigens. The newly discovered epitopes can be exploited for immune intervention against processing-deficient tumors through adoptive T-cell transfer or peptide vaccination., Author(s): Thorbald van Hall (corresponding author) [1, 8]; Elisabeth Z Wolpert [2, 8]; Peter van Veelen [1, 3, 8]; Sandra Laban [1]; Michael van der Veer [1]; Marjet Roseboom [1]; [...]

Published
2006
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35. Dendritic cell immunotherapy: mapping the way

Author

Figdor, Carl G, de Vries, I Jolanda M, Lesterhuis, W Joost, and Melief, Cornelis J M

Abstract

Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system, with the potential to either stimulate or inhibit immune responses. Exploiting the immune-regulatory capacities of dendritic cells holds great promise for the treatment of cancer, autoimmune diseases and the prevention of transplant rejection. Although early clinical trials indicate that DC vaccines can induce immune responses in some cancer patients, careful study design and use of standardized clinical and immunological criteria are needed., Author(s): Carl G Figdor (corresponding author) [1]; I Jolanda M de Vries [1]; W Joost Lesterhuis [2]; Cornelis J M Melief [3] DCs are antigen-presenting cells with the unique ability [...]

Published
2004
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36. IFN‐γ‐induced PD‐L1 expression on human melanocytes is impaired in vitiligo.

Author

Willemsen, Marcella, Krebbers, Gabrielle, Tjin, Esther P. M., Willemsen, Karin J., Louis, Alesha, Konijn, Veronique A. L., Narayan, Vidhya S., Post, Nicoline F., Bakker, Walbert J., Melief, Cornelis J. M., Bekkenk, Marcel W., and Luiten, Rosalie M.

Subjects
VITILIGO, PROGRAMMED death-ligand 1, INTERFERON gamma, MELANOCYTES, TYPE I interferons, PROGRAMMED cell death 1 receptors
Abstract

Mounting evidence shows that the PD‐1/PD‐L1 axis is involved in tumor immune evasion. This is demonstrated by anti‐PD‐1 antibodies that can reverse tumor‐associated PD‐L1 to functionally suppress anti‐tumor T‐cell responses. Since type I and II interferons are key regulators of PD‐L1 expression in melanoma cells and IFN‐γ‐producing CD8+ T cells and IFN‐α‐producing dendritic cells are abundant in vitiligo skin, we aimed to study the role of PD‐1/PD‐L1 signalling in melanocyte destruction in vitiligo. Moreover, impaired PD‐1/PD‐L1 function is observed in a variety of autoimmune diseases. It is, therefore, hypothesized that manipulating PD‐1/PD‐L1 signalling might have therapeutic potential in vitiligo. The PD‐1+ T cells were abundantly present in situ in perilesional vitiligo skin, but expression of PD‐L1 was limited and confined exclusively to dermal T cells. More specifically, neither melanocytes nor other epidermal skin cells expressed PD‐L1. Exposure to IFN‐γ, but also type I interferons, increased PD‐L1 expression in primary melanocytes and fibroblasts, derived from healthy donors. Primary human keratinocytes only showed increased PD‐L1 expression upon stimulation with IFN‐γ. More interestingly, melanocytes derived from non‐lesional vitiligo skin showed no PD‐L1 upregulation upon IFN‐γ exposure, while other skin cells displayed significant PD‐L1 expression after exposure. In a vitiligo skin explant model, incubation of non‐lesional vitiligo skin with activated (IFN‐γ‐producing) T cells from vitiligo lesions was previously described to induce melanocyte apoptosis. Although PD‐L1 expression was induced in epidermal cells in these explants, this induction was completely absent in melanocytes. The lack of PD‐L1 upregulation by melanocytes in the presence of IFN‐γ‐producing T cells shows that melanocytes lack protection against T‐cell attack during vitiligo pathogenesis. Manipulating PD‐1/PD‐L1 signalling may, therefore, be a therapeutic option for vitiligo patients. [ABSTRACT FROM AUTHOR]

Published
2022
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39. Combination vaccine based on citrullinated vimentin and enolase peptides induces potent CD4-mediated anti-tumor responses

Author

Brentville, Victoria A, primary, Metheringham, Rachael L, additional, Daniels, Ian, additional, Atabani, Suha, additional, Symonds, Peter, additional, Cook, Katherine W, additional, Vankemmelbeke, Mireille, additional, Choudhury, Ruhul, additional, Vaghela, Poonam, additional, Gijon, Mohamed, additional, Meiners, Ghislaine, additional, Krebber, Willem-Jan, additional, Melief, Cornelis J M, additional, and Durrant, Lindy G, additional

Published
2020
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40. Strong vaccine responses during chemotherapy are associated with prolonged cancer survival

Author

Melief, Cornelis J. M., primary, Welters, Marij J. P., additional, Vergote, Ignace, additional, Kroep, Judith R., additional, Kenter, Gemma G., additional, Ottevanger, Petronella B., additional, Tjalma, Wiebren A. A., additional, Denys, Hannelore, additional, van Poelgeest, Mariette I. E., additional, Nijman, Hans W., additional, Reyners, Anna K. L., additional, Velu, Thierry, additional, Goffin, Frederic, additional, Lalisang, Roy I., additional, Loof, Nikki M., additional, Boekestijn, Sanne, additional, Krebber, Willem Jan, additional, Hooftman, Leon, additional, Visscher, Sonja, additional, Blumenstein, Brent A., additional, Stead, Richard B., additional, Gerritsen, Winald, additional, and van der Burg, Sjoerd H., additional

Published
2020
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43. A strong HPV-specific T-cell response after chemo-immunotherapy for advanced cervical cancer is associated with prolonged survival

Author

Melief, Cornelis J. M., Welters, Marij J., Vergote, Ignace, Kroep, Judith R., Kenter, Gemma G., Ottevanger, Nelleke, Tjalma, Wiebren A., Denys, Hannelore, van Poelgeest, Mariette, Nijman, Hans W., Reyners, Anna K., Velu, Thierry, Goffin, Frederic, Lalisang, Roy, Krebber, Willem-Jan, Hooftman, Leon, Visscher, Sonja, Blumenstein, Brent A., Stead, Richard B., Gerritsen, Winald, van der Burg, Sjoerd, Targeted Gynaecologic Oncology (TARGON), Translational Immunology Groningen (TRIGR), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Published
2019

46. Cd8 T-cell recognition of human 5T4 oncofetal antigen

Author

Smyth, Lucy JC, Elkord, Eyad, Taher, Taher E.I., Jiang, Hui-Rong, Burt, Deborah J., Clayton, Alison, van Veelen, Peter A., de Ru, Arnoud, Ossendorp, Ferry, Melief, Cornelis J. M., Drijfhout, Jan W., Dermime, Said, Hawkins, Robert E., and Stern, Peter L.

Published
2006
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49. Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors

Author

Quakkelaar, Esther D., Redeker, Anke, Haddad, Elias K., Harari, Alexandre, McCaughey, Stella Mayo, Duhen, Thomas, Filali-Mouhim, Abdelali, Goulet, Jean-Philippe, Loof, Nikki M., Ossendorp, Ferry, Perdiguero, Beatriz, Heinen, Paul, Gomez, Carmen E., Kibler, Karen V., Koelle, David M., Sékaly, Rafick P., Sallusto, Federica, Lanzavecchia, Antonio, Pantaleo, Giuseppe, Esteban, Mariano, Tartaglia, Jim, Jacobs, Bertram L., Melief, Cornelis J. M., Quakkelaar, Esther D., Redeker, Anke, Haddad, Elias K., Harari, Alexandre, McCaughey, Stella Mayo, Duhen, Thomas, Filali-Mouhim, Abdelali, Goulet, Jean-Philippe, Loof, Nikki M., Ossendorp, Ferry, Perdiguero, Beatriz, Heinen, Paul, Gomez, Carmen E., Kibler, Karen V., Koelle, David M., Sékaly, Rafick P., Sallusto, Federica, Lanzavecchia, Antonio, Pantaleo, Giuseppe, Esteban, Mariano, Tartaglia, Jim, Jacobs, Bertram L., and Melief, Cornelis J. M.

Abstract

Attenuated poxviruses are safe and capable of expressing foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses in vitro from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs), RNA expression arrays, HIV gag expression and crosspresentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferoninduced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activationof pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIVspecific memory CD8 T-cells in vitro. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines.

Published
2019

50. Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C

Author

Gómez, Carmen Elena, Perdiguero, Beatriz, Jiménez, Victoria, Filali-Mouhim, Abdelali, Ghneim, Khader, Haddad, Elias K., Quakkerlaar, Esther D., Delaloye, Julie, Harari, Alexandre, Roger, Thierry, Dunhen, Thomas, Sékaly, Rafick P., Melief, Cornelis J. M., Calandra, Thierry, Sallusto, Federica, Lanzavecchia, Antonio, Wagner, Ralf, Pantaleo, Giuseppe, Esteban, Mariano, Gómez, Carmen Elena, Perdiguero, Beatriz, Jiménez, Victoria, Filali-Mouhim, Abdelali, Ghneim, Khader, Haddad, Elias K., Quakkerlaar, Esther D., Delaloye, Julie, Harari, Alexandre, Roger, Thierry, Dunhen, Thomas, Sékaly, Rafick P., Melief, Cornelis J. M., Calandra, Thierry, Sallusto, Federica, Lanzavecchia, Antonio, Wagner, Ralf, Pantaleo, Giuseppe, and Esteban, Mariano

Abstract

Based on the partial efficacy of the HIV/AIDS Thai trial (RV144) with a canarypox vector prime and protein boost, attenuated poxvirus recombinants expressing HIV-1 antigens are increasingly sought as vaccine candidates against HIV/AIDS. Here we describe using systems analysis the biological and immunological characteristics of the attenuated vaccinia virus Ankara strain expressing the HIV-1 antigens Env/Gag-Pol-Nef of HIV-1 of clade C (referred as MVA-C). MVA-C infection of human monocyte derived dendritic cells (moDCs) induced the expression of HIV-1 antigens at high levels from 2 to 8 hpi and triggered moDCs maturation as revealed by enhanced expression of HLA-DR, CD86, CD40, HLA-A2, and CD80 molecules. Infection ex vivo of purified mDC and pDC with MVA-C induced the expression of immunoregulatory pathways associated with antiviral responses, antigen presentation, T cell and B cell responses. Similarly, human whole blood or primary macrophages infected with MVA-C express high levels of proinflammatory cytokines and chemokines involved with T cell activation. The vector MVA-C has the ability to cross-present antigens to HIV-specific CD8 T cells in vitro and to increase CD8 T cell proliferation in a dose-dependent manner. The immunogenic profiling in mice after DNA-C prime/MVA-C boost combination revealed activation of HIV-1-specific CD4 and CD8 T cell memory responses that are polyfunctional and with effector memory phenotype. Env-specific IgG binding antibodies were also produced in animals receiving DNA-C prime/MVA-C boost. Our systems analysis of profiling immune response to MVA-C infection highlights the potential benefit of MVA-C as vaccine candidate against HIV/AIDS for clade C, the prevalent subtype virus in the most affected areas of the world.

Published
2019

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