Vaccine Consortium Research Articles

Equatorial Guinea on a very high alert as Marburg virus spreads: an urgent rising concern

The filoviridae family of viruses, which comprises the more well-known Ebola virus, also includes the Marburg virus (MARV). An African fruit bat is thought to harbor the virus, where following laboratory workers in Frankfurt, Germany, Marburg, Germany, and Belgrade, Yugoslavia (now Serbia), contracted the MARV leading to its initial identification in 1967. Humans may contract the virus and exhibit the syndrome, as can other primates1. Notwithstanding disagreements on the origin, the majority of the evidence refers to Uganda2. In addition to the Democratic Republic of the Congo, Angola, Uganda, the United States, Guinea, Uganda, and Ghana, outbreaks have also been documented in South Africa, Kenya, and Angola since 1967. Equatorial Guinea only recently confirmed its first MARV epidemic outbreak on February 13, 20231. Humans may contract the virus through direct contact with infected individuals alongside bat saliva, urine, or excrement. Contact with said infected animals, such as primates, may also cause human infection3. Hy viral transmission with blood, saliva, or other bodily fluids of the infected individual, the virus may disseminate within populations. Possessing a mortality rate of ~90%, the MARV infection has symptoms that are comparable to those of other viral hemorrhagic fevers, resulting in major bleeding, shock, organ failure, and death3. There are presently no clinically authorized treatments or vaccines to prevent or treat MARV disease, respectively. Palliation is occasionally considered when conservative measures have failed3. The current Marburg virus outbreak in Equatorial Guinea and efforts to curb the virus The deaths are said to have occurred between January 7 and February 7. Moreover, as of 13 February 2023, there are 16 suspected cases of Marburg virus disease (MVD) in Equatorial Guinea4. Meanwhile, 2 potential Marburg disease cases were discovered on Monday in Olamze, a commune near the Equatorial Guinea border, by Cameroonian authorities5. In response, WHO convened the MARV vaccine consortium to evaluate several potential vaccine candidates. Also, the WHO is collaborating with the government of Equatorial Guinea to provide rapid emergency response services and has deployed experts to assist with MARV epidemiology, case management, infection prevention, laboratory, and risk communication4. Recommendations Equatorial Guinea took more than a month to announce an outbreak after the reported date of the first mortality caused by the MARV. This highlights a need for rapid diagnosis and a capacity limitation in public health. The western part of Equatorial Guinea needs immediate action to bolster its monitoring system and limit additional virus transmission through contact tracing. In addition, as there are 2 probable cases in Cameroon, immediate action must be enforced to halt the local dissemination of the virus. Further, providing guidance to medical personnel concerning case management alongside access to appropriate diagnostic testing will further dissipate viral transmission. We must reinforce the paramount importance of Personal Protective equipment in health care professionals as is essential for limiting viral spread. The MARV vaccine needs to be developed, and antivirals specific to the virus need to be produced as quickly as possible. To conclude, the government’s efforts towards making sure the public has access to timely, reliable information about the virus should be strengthened, at the same time it would also be beneficial for the global community to launch campaigns to raise public knowledge about the MARV globally through the mass and social medias. Ethical approval None. Sources of funding None. Author contribution None. Conflict of interest disclosures The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) None. Guarantor None.

OPENCORONA: lessons learned from a pandemic vaccine consortium

OPENCORONA: lessons learned from a pandemic vaccine consortium

Abstract A020: Immunomonitoring for actively personalized peptide vaccines (APVACs) during immunotherapeutic treatment of glioblastoma

Abstract Cancer immunotherapy to gliomas has so far failed to show encouraging results, as gliomas are rarely mutated and show various mechanisms of immune escape. To improve therapy to these type of cancer, the Glioma Actively Personalized Vaccine Consortium (GAPVAC) integrated a highly personalized peptide vaccine approach into glioblastoma standard of care treatment combining neoepitope and nonmutated tumor antigens to exploit the full repertoire of tumor antigens. In this phase I clinical trial fifteen patients received two different types of personalized peptide vaccines (APVAC1 and APVAC2), that were selected based on transcriptome, immunopeptidome and mutational analysis of the patient’s individual tumors. While APVAC1 vaccines were composed of nonmutated tumor antigens selected in a warehouse-based approach, APVAC2 vaccines primarily targeted neoepitopes. Both vaccines were used in combination with poly-ICLC and GM-CSF as adjuvants and demonstrated expected safety profile and outstanding Immunogenicity. Immunomonitoring of APVAC1 peptides was carried out using a combinatorial ex vivo Class I 2D multimer (2DMM) and Class II intracellular cytokine staining (ICS) assay with an outstanding sensitivity to detect even one peptide-specific cell in one million of CD4 or CD8 T-cells. Nonmutated APVAC1 class I peptides showed induction of persistent CD8 T-cell responses, mainly consisting of a highly favorable central memory phenotype (CM). Furthermore, APVAC1 class II peptides demonstrated induction of polyfunctional CD4 T-cells predominantly of a type 1 T helper cell (TH1) phenotype. Notably, an APVAC1 class II specific T-cell response was detected in tumor-infiltrating lymphocyte (TIL) fraction obtained from resection of one patient. On the other side, immune responses to APVAC2 peptides were analyzed using a pan-ICS assay including a single in vitro sensitization step to analyze a broad array of cytokines produced by CD4 T helper (TH) cells and CD8 CTLs in parallel. APVAC2 peptides showed excellent immunogenicity and induced potent and multifunctional CD4 T-cell responses, mostly of a TH1 phenotype that often concurred with CTL responses. Furthermore, the induction of APVAC1-specific CD8 memory cells, as a marker for the potency of the vaccine-induced immune responses, reversely correlated with the baseline frequencies of regulatory T-cells (Treg). Taken together, actively personalized peptide vaccines (APVACs) were highly immunogenic and induced sustained responses of a highly favorable CD4 and CD8 T-cell phenotype. The vaccination showed the expected safety profile and the approach was feasible, even in this highly individualized setting. Therefore, the APVAC vaccination approach clearly represents a step forward on the path to bring the benefit of immunotherapy to glioblastoma patients. Citation Format: Alexander Ulges, Norbert Hilf, Wolfgang Wick, Michael Platten, Pierre-Yves Dietrich, Katrin Frenzel, Arie Admon, Sjoerd S.H. van der Burg, Andreas von Deimling, Per thor Straten, Cecile Gouttefangeas, Judith R. Kroep, Francisco Martínez-Ricarte, Hideo Okada, Christian H. Ottensmeier, Berta Ponsati, Hans S. Poulsen, Stefan Stevanovic, Ghazaleh Tabatabai, Hans-Georg Rammensee, Ugur Sahin, Dominik Maurer, Regina Mendrzyk. Immunomonitoring for actively personalized peptide vaccines (APVACs) during immunotherapeutic treatment of glioblastoma [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A020.

Abstract 2654: GAPVAC-101 phase I trial: First data of an innovative actively personalized peptide vaccination trial in patients with newly diagnosed glioblastoma

Abstract The Glioma Actively Personalized Vaccine Consortium (GAPVAC; funded by the European Union Framework 7 Program) aims at treating newly diagnosed glioblastoma (GB) patients with two distinct actively personalized vaccines (APVACs). Resected tumor material is analyzed for multiple biomarkers to characterize the tumor in depth and to enable the design of APVACs tailored to each individual patient: Tumor-specific mutations, the HLA peptidome and gene expression profile are assessed by next-generation sequencing, mass spectrometry and RNA microarray analysis, respectively. Further, the patient-individual immune status is investigated by assessment of leukapheresis samples utilizing an in vitro immunogenicity platform. Data are integrated to define two distinct APVACs for each patient: APVAC1 is composed of up to ten peptides selected from a pre-manufactured “warehouse”. The warehouse contains 59 HLA class I-binding and three class II-binding tumor-associated peptides frequently over-presented in GB. APVAC2 is composed of one or two peptides that are de novo synthesized for a given patient and preferentially represent mutation-bearing neo-epitopes. After a preparation phase in which the warehouse was generated and setup of APVAC selection and manufacturing processes took place, the GAPVAC-101 phase I clinical trial was initiated. Primary endpoints of the study are assessment of safety, feasibility of APVAC manufacturing and biological activity. The trial is conducted at six European centers and recruits HLA-A*02:01 or A*24:02-positive patients with newly diagnosed GB after gross total resection. Patients receive APVAC1 and APVAC2 vaccinations plus immunomodulators (poly-ICLC and GM-CSF) three and six months post study enrolment, respectively, and concurrent to maintenance temozolomide (TMZ). As of November 2015, 11 patients have been enrolled, of whom six already received APVAC vaccines. Composition and manufacturing are ongoing for four patients. All APVACs were generated in time without ultimate failures. APVAC1 vaccines differ substantially with 31 out of 59 warehouse peptides have been selected at least once, indicating the need for personalization due to tumor heterogeneity even for non-mutated epitopes. In patients’ tumor samples an average of 40 non-synonymous mutations (including known driver mutations) were identified. Injection site reactions were the most frequent toxicities so far. One brain edema (Grade 3) and one allergic reaction (Grade 4)were observed, both potentially related to the vaccinations. First data on biological activity of APVACs and updated clinical data will be presented at the Annual Meeting. In conclusion, the GAPVAC concept has been successfully translated into the clinics and so far demonstrated to be safe and feasible with its level of personalization matching the observed tumor heterogeneity. Citation Format: Norbert Hilf, Katrin Frenzel, Sabrina Kuttruff-Coqui, Sandra Heesch, Sebastian Kreiter, Arie Admon, Valesca Bukur, Sjoerd van der Burg, Cecile Gouttefangeas, Judith R. Kroep, Marij Schoenmaekers-Welters, Jordi Piro, Berta Ponsati, Hans Skovgaard Poulsen, Ulrik Lassen, Francisco Martinez-Ricarte, Jordi Rodon, Juan Sahuquillo, Monika Stieglbauer, Stefan Stevanovic, Per thor Straten, Marco Skardelly, Ghazaleh Tabatabai, Michael Platten, David Capper, Andreas von Deimling, Valérie Dutoit, Hideho Okada, Christian Ottensmeier, Randi Kristina Feist, Jens Fritsche, Karoline Laske, Peter Lewandrowski, Martin Löwer, Regina Mendryzk, Miriam Meyer, Carsten Reinhardt, Bernhard Rössler, Anna Paruzynski, Nina Pawlowski, Colette Song, Stevermann Lea, Toni Weinschenk, Christoph Huber, Hans-Georg Rammensee, Pierre-Yves Dietrich, Wick Wolfgang, Ugur Sahin, Harpreet Singh-Jasuja. GAPVAC-101 phase I trial: First data of an innovative actively personalized peptide vaccination trial in patients with newly diagnosed glioblastoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2654.

Cattle tick vaccine researchers join forces in CATVAC.

A meeting sponsored by the Bill & Melinda Gates Foundation was held at the Avanti Hotel, Mohammedia, Morocco, July 14–15, 2015. The meeting resulted in the formation of the Cattle Tick Vaccine Consortium (CATVAC).

An HIV-1 clade A/E DNA prime, recombinant fowlpox virus boost vaccine is safe, but non-immunogenic in a randomized phase I/IIa trial in Thai volunteers at low risk of HIV infection

NCHECR is funded by the Australian Government Department of Health & Ageing and is affiliated with the Faculty of Medicine, The University of New South Wales. The vaccines were designed with the assistance of NIH-NIAID-DAIDS HVDDT Award N01-AI-05395. The authors would like to thank Wadchara Pumpradit for his assistance in the preparation and initial drafting of trial protocols and regulatory documents. We also wish to thank members of the Australia Thai HIV Vaccine Consortium including the CSIRO, Australian National University, University of Melbourne, Australian Federation of AIDS Organisations, National Centre in HIV Social Research, University of New South Wales for the design and manufacture of vaccines and assistance with study protocol drafting and initiation. We would like to acknowledge Ormrudee Rit-im, Wendy Lee, Noorul Absar, Charles Tran, Pitch Boonrak and Ekkasit Thodsanit for database and statistical assistance, Nounpen Sangthong, Narumon Subsri, Kanitta Pussadee and Peeraporn Keaw-on for clinical care, Parinya Sutheerasak for pharmacy expertise and Meeling Munier, Kate Merlin, Supranee Buranapraditkun, Pornsupa Chatkulkawin for their laboratory input. Salaries for those working in the Vaccine and Cellular Immunology Laboratory were kindly supported in part by grants from the National Center for Genetic Engineering and Biotechnology, Thailand.

Harmonization guidelines for HLA-peptide multimer assays derived from results of a large scale international proficiency panel of the Cancer Vaccine Consortium

PurposeThe Cancer Vaccine Consortium of the Cancer Research Institute (CVC-CRI) conducted a multicenter HLA-peptide multimer proficiency panel (MPP) with a group of 27 laboratories to assess the performance of the assay.Experimental designParticipants used commercially available HLA-peptide multimers and a well characterized common source of peripheral blood mononuclear cells (PBMC). The frequency of CD8+ T cells specific for two HLA-A2-restricted model antigens was measured by flow cytometry.The panel design allowed for participants to use their preferred staining reagents and locally established protocols for both cell labeling, data acquisition and analysis.ResultsWe observed significant differences in both the performance characteristics of the assay and the reported frequencies of specific T cells across laboratories. These results emphasize the need to identify the critical variables important for the observed variability to allow for harmonization of the technique across institutions.ConclusionsThree key recommendations emerged that would likely reduce assay variability and thus move toward harmonizing of this assay. (1) Use of more than two colors for the staining (2) collect at least 100,000 CD8 T cells, and (3) use of a background control sample to appropriately set the analytical gates. We also provide more insight into the limitations of the assay and identified additional protocol steps that potentially impact the quality of data generated and therefore should serve as primary targets for systematic analysis in future panels. Finally, we propose initial guidelines for harmonizing assay performance which include the introduction of standard operating protocols to allow for adequate training of technical staff and auditing of test analysis procedures.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-009-0681-z) contains supplementary material, which is available to authorized users.

Lessons from randomized phase III studies with active cancer immunotherapies – Outcomes from the 2006 Meeting of the Cancer Vaccine Consortium (CVC)

After years of effort to develop active cancer immunotherapies, seven candidate products achieved promising results in phase I/II studies that triggered phase III randomized studies. One candidate to date has received an approvable letter from the United States Food and Drug Administration (FDA), defining a clear path to licensure for sipuleucel-T (Provenge, Dendreon) within the next couple of years. The other phase III studies failed to achieve statistical criteria for some or all of the critical endpoints. Yet, there is widespread recognition that using a patient's own immune system to target and destroy cancer cells may offer an effective biological therapy with less toxicity than presently available anti-cancer therapies, and several candidates are still being evaluated in clinical studies. This review summarizes the lessons learned from these case studies, evaluates scientific, study design, and business factors that can affect study outcomes, identifies common challenges faced by sponsors developing these innovative therapies, and provides considerations for future study designs that may increase the likelihood of success.

Results and harmonization guidelines from two large-scale international Elispot proficiency panels conducted by the Cancer Vaccine Consortium (CVC/SVI)

The Cancer Vaccine Consortium of the Sabin Vaccine Institute (CVC/SVI) is conducting an ongoing large-scale immune monitoring harmonization program through its members and affiliated associations. This effort was brought to life as an external validation program by conducting an international Elispot proficiency panel with 36 laboratories in 2005, and was followed by a second panel with 29 participating laboratories in 2006 allowing for application of learnings from the first panel. Critical protocol choices, as well as standardization and validation practices among laboratories were assessed through detailed surveys. Although panel participants had to follow general guidelines in order to allow comparison of results, each laboratory was able to use its own protocols, materials and reagents. The second panel recorded an overall significantly improved performance, as measured by the ability to detect all predefined responses correctly. Protocol choices and laboratory practices, which can have a dramatic effect on the overall assay outcome, were identified and lead to the following recommendations: (A) Establish a laboratory SOP for Elispot testing procedures including (A1) a counting method for apoptotic cells for determining adequate cell dilution for plating, and (A2) overnight rest of cells prior to plating and incubation, (B) Use only pre-tested serum optimized for low background: high signal ratio, (C) Establish a laboratory SOP for plate reading including (C1) human auditing during the reading process and (C2) adequate adjustments for technical artifacts, and (D) Only allow trained personnel, which is certified per laboratory SOPs to conduct assays. Recommendations described under (A) were found to make a statistically significant difference in assay performance, while the remaining recommendations are based on practical experiences confirmed by the panel results, which could not be statistically tested. These results provide initial harmonization guidelines to optimize Elispot assay performance to the immunotherapy community. Further optimization is in process with ongoing panels.

HIV vaccine consortium established using US NIAID funds

HIV vaccine consortium established using US NIAID funds

Polish Vaccine Consortium--a new national player in the influenza research.

Polish Vaccine Consortium--a new national player in the influenza research.