Immunology and Infectious Disease Commons^™

Evaluation Of Tick-Derived Peptides For Transmission-Blocking Vaccine Candidates, Madelyn Futral

Honors Theses

The lack of effective preventive measures for tick-borne diseases represents a major public health challenge. Transmission-blocking vaccines targeting tick molecules essential for feeding or reproduction could provide a sustainable and broad-spectrum solution. In this study, we evaluated two tick-derived proteins as potential vaccine antigens, subolesin, a key regulator of blood-feeding and cellular processes, and vitellogenin, a protein involved in egg development. Using bioinformatic tools, we identified immunogenic peptide sequences from each protein and chemically conjugated them to virus-like particles (VLPs) to enhance antigen presentation. C57BL/6 mice were immunized intradermally with VLP-peptide conjugates, followed by a booster dose. Blood and spleen …

Immunogenicity And Efficacy Of A Rabies-Based Vaccine Against Highly Pathogenic Influenza H5n1 Virus, Nir Paran, Christoph Wirblich, Randy Albrecht, Leila Zabihi Diba, Alessandro Tarquinio, Drishya Kurup, Charalambos C. Solomides, Adolfo García-Sastre, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

The recent spillover of highly pathogenic influenza A/H5N1 (HPAI-H5N1) viruses to cattle, other mammals, and humans poses a major risk to animal and human health. Virus adaptation to new species highlights the need for effective vaccines for animals and humans. We recently developed a rabies virus-based H5 vaccine encoding the HPAI-H5 antigen and presenting it on the surface of the rabies virus particle. To test the immunogenicity and efficacy of the vaccine in eliciting systemic and mucosal immune response, we vaccinated mice intramuscularly or intranasally with either live or inactivated and adjuvanted vaccine. The vaccine elicited neutralizing antibodies against RABV …

Identifying Correlates Of Protection Of A Pneumonic Plague Vaccine., Caleb Samuel Whitley

Electronic Theses and Dissertations

Pneumonic plague is caused by inhalation of the bacterial pathogen Yersinia pestis. The immune response during Pneumonic plague occurs in two phases; an initial asymptomatic phase followed by a highly inflammatory and destructive phase resulting in 100% mortality if left untreated. The rapid onset of severe disease following the asymptomatic phase makes it difficult to administer antibiotics in time to prevent lethal outcomes. Therefore, the development of an effective vaccine is likely needed to combat pneumonic plague in areas of the world where Y. pestis remains endemic. One candidate subunit vaccine is protective in mice, a natural host for …

Next-Generation Salmonella Inactivated Vaccine Platforms And Phytobiotic-Modulated Immune Responses In Poultry, Santiago Uribe Diaz

Graduate Theses and Dissertations

Here, a comprehensive understanding of immune responses triggered by either a multimeric CD40 receptor-agonistic DNA aptamer-based or mannosylated chitosan-based Salmonella Enteritidis inactivated vaccine platforms, along with phytobiotic supplementation as an immune modulatory strategy in response to Salmonella lipopolysaccharides, is presented. This dissertation supports the development of next-generation Salmonella vaccine platforms that simultaneously stimulate both protective cell-mediated and humoral immune responses, while indicating the potential immunomodulatory effects of phytobiotics supplementation to reduce the immunological impact of Salmonella lipopolysaccharides in chickens. The first chapter describes that both vaccine platforms administered in broiler chickens initiated local inflammatory responses, recruiting heterophils and macrophages from …

Vaccination Against Onchocerca Volvulus Induces Igg-Mediated Protective Immunity Dependent On Neutrophils And Complement, Nathan M. Ryan, Jessica A. Hess, Mohini Nakhale, Annabel A. Ferguson, William Stump, Sara Belko, Rachel Monane, Robert S. Pugliese, Nikolai Petrovsky, Benjamin L. Makepeace, Sean A. Gray, Darrick Carter, Sara Lustigman, David Abraham

Department of Microbiology and Immunology Faculty Papers

Onchocerciasis remains a significant cause of morbidity and economic loss in sub-Saharan Africa. Despite the existence of effective therapeutics, a prophylactic vaccine targeting the etiologic agent, Onchocerca volvulus, is needed to control ongoing disease and transmission. Mice were vaccinated against O. volvulus with a fusion of the recombinant antigens Ov-103 and Ov-RAL-2 (Ov-FUS-1) with Advax-CpG adjuvant. Immunized mice developed protective immunity with the killing of third-stage larvae (L3) within 36 h of challenge infection. IgG from immunized mice passively transferred protective immunity to naïve mice, indicating that antigen-specific IgG mediated parasite elimination. Neutrophils were the most abundant subset of immune …

Development Of A Multi-Epitope Peptide Vaccine Against Monkeypox Virus: Immunoinformatics Analysis For South East Asian Hla Alleles, Nelson Chandra, Mochammad Aqilah Herdiansyah, Viol Dhea Kharisma, Arif Nur Muhammad Ansori, Arli Aditya Parikesit

Makara Journal of Science

The monkeypox virus (MPXV), a DNA virus causing zoonotic disease, poses major global public health challenges, with mortality rates between 3%–6%. Although smallpox vaccines provide partial cross-protection, there is a critical need for a dedicated, effective monkeypox (mpox) vaccine. This study aimed to design a multi-epitope peptide-based vaccine specifically adapted to the HLA allele profiles common in Southeast Asian populations, where MPXV cases are rising. Using immunoinformatics, we screened for and detected B and T cell epitopes from the MPXV cell surface antigen and IFN-alpha/beta receptor proteins. The vaccine design was validated through a rigorous evaluation of its antigenicity, immunogenicity, …

Evaluation Of The Efficacy Of Synthetic Glycovaccines Against Both Murine Acute Chagas Disease And Cutaneous Leishmaniasis, Colin D. Knight

Open Access Theses & Dissertations

Chagas disease (CD) and cutaneous leishmaniasis (CL) are neglected tropical diseases caused by the protozoan trypanosomatids, Trypanosoma cruzi and Leishmania spp., respectively. There are approximately 6-8 million people infected with T. cruzi worldwide and ~300,000 people in the US. Between 700,000 and 1.2 million new cases of CL occur worldwide yearly. The approved chemotherapies for both diseases are partially effective and may cause serious adverse events, resulting in premature treatment interruption. Moreover, no effective vaccine for either disease is available. Therefore, developing a vaccine that would provide effective cross-protection against both diseases would provide a cost-effective alternative to the existing …

Sars-Cov-2: Tale Of A Microscopic Murderer, Josiah P. Garner

Quest

Independent Study

Research in progress for BIOL1406: Biology for Science Majors I

Faculty Mentor: Amina Tassa, Ph.D.

I am delighted to introduce Josiah Garner’s “SARS-CoV-2: Tale of a Microscopic Murderer.” This independent study assignment explores the impact of a novel, deadly, and worldwide virus. The assignment also examines the fast development of vaccines to control the spread and reduce the symptoms of the virus.

Josiah’s paper focuses on the early history of the emergence of COVID-19, the world response, and vaccine development. He demonstrates critical thinking skills and effectively utilizes various research methods to obtain and communicate his information. Josiah …

Mycobacterium Avium Subsp. Paratuberculosis Candidate Vaccine Strains Are Pro-Apoptotic In Raw264.7murinemacrophages, Raul G. Barletta, John P. Bannantine, Judith R. Stabel, Ezhumalai Muthukrishnan, Dirk Anderson, Enakshy Dutta, Vamsi Manthena, Mostafa Hanafy, Denise K. Zinniel

School of Veterinary and Biomedical Sciences: Faculty Publications

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne’s disease, a severe gastroenteritis of ruminants. This study developed a model cell culture system to rapidly screen MAP mutants with vaccine potential for apoptosis. Two wild-type strains, a transposon mutant, and two deletion mutant MAP strains (MOI of 10 with 1.2 × 10⁶ CFU) were tested in murine RAW 264.7 macrophages to determine if they induce apoptosis and/or necrosis. Both deletion mutants were previously shown to be attenuated and immunogenic in primary bovine macrophages. All strains had similar growth rates, but cell morphology indicated that both deletion mutants …

Prevalence Of Sars-Cov-2 Antibodies In Liberty University Student Population, Emily Bonus

Senior Honors Theses

In 2020, the virus SARS-CoV-2 gained attention as it spread around the world. Its antibodies are poorly understood, and little research focuses on those with few COVID-19 complications yet large numbers of close contacts: university students. This longitudinal study recorded SARS-CoV-2 antibody presence in 107 undergraduate Liberty University students twice during early 2021. After extensive data cleaning and the application of various statistical tests and ANOVAs, the data seems to show that in the case of COVID-19 infections, SARS-CoV-2 IgM antibodies are immediately produced, and then IgG antibodies follow later. However, the COVID-19 vaccine causes the production of both IgM …

Antibody-Dependent Enhancement Activity Of A Plant-Made Vaccine Against West Nile Virus, Amber M. Paul, Haiyan Sun, Dhiraj Acharya, Huafang Lai, Junyun He, Fengwei Bai, Qiang Chen

Publications

West Nile virus (WNV) causes annual outbreaks globally and is the leading cause of mosquito-borne disease in Unite States. In the absence of licensed therapeutics, there is an urgent need to develop effective and safe human vaccines against WNV. One of the major safety concerns for WNV vaccine development is the risk of increasing infection by related flaviviruses in vaccinated subjects via antibody-dependent enhancement of infection (ADE). Herein, we report the development of a plant-based vaccine candidate that provides protective immunity against a lethal WNV challenge mice, while minimizes the risk of ADE for infection by Zika (ZIKV) and dengue …

The Psychology Of Science Denialism And Lessons For Public Health Authorities, Brenna Moreno, Molly J. Walker Wilson

All Faculty Scholarship

As it wreaked tragedy on the world, the outbreak of COVID-19 helped expose a pandemic of a different kind, one steeped in distrust and contrarianism. This movement, termed science denialism, has been lurking and undermining public health efforts for decades. Specifically, it is “the employment of rhetorical arguments to give the appearance of legitimate debate where there is none, an approach that has the ultimate goal of rejecting a proposition on which a scientific consensus exists.” Unlike skepticism, which is “doubt as to the truth of something” and works to progress both science and society, denialism is characterized by individuals’ …

Generation Of Chimeric Rhinoviruses Presenting Sars-Cov-2 Broadly Neutralizing Epitopes And Their Antigenicity Characterization, Danish Ansari

Biotechnology Theses

The global COVID pandemic is not yet fully under control as there were over 21 million new cases of SARS-CoV-2 infections and over 50,000 deaths globally as of January of 2022. A heavily mutated variant of concern, Omicron is responsible for most of these cases which demands an urgency for a new vaccine. NIH reports over 180 vaccine candidates that use various strategies currently in development. However, a recurring concern with these vaccines is that the continuous viral mutations decrease the efficacy of vaccines. Therefore, we proposed to construct a human rhinovirus (HRV) based chimeric virus containing highly conserved, broadly …

The Development Of A New Pertussis Booster Formulation Via The Implementation Of New Adjuvants And Utilization Of Alternate Routes Of Administration, Megan Ashley Dejong

Graduate Theses, Dissertations, and Problem Reports (ETD)

Pertussis (whooping cough) is a respiratory disease caused by airborne transmission of the Gram-negative bacterium, Bordetella pertussis. Prior to the development of the first pertussis vaccines (whole cell (wP) vaccines), the incidence of pertussis was in the hundreds of thousands of cases per year, which led to the death of many children, as the infection is most severe in younger populations. Thankfully, the wP formulation resulted in a dramatic decrease in the number of annual pertussis cases, nearly eradicating the disease. However, as wP contained the whole B. pertussis bacterium (and its lipooligosaccharide (LOS)), reactogenicity issues became apparent, leading …

Nanofabrication For Precision Vaccinology, Karen Zagorski

Theses & Dissertations

Vaccines are among the most effective and safe therapeutics known to mankind. Historically the approach to the creation of new vaccines has been dominated by empirical research, trial, and error. This thesis focuses on the more modern, rational approaches to vaccinology based on the current understanding of the inner workings of the immune system. We used nanotechnology for the generation of novel immunogens, addressed several challenges, and characterized the immune responses.

The preparation, characterization, and troubleshooting of several vaccines against dimeric amyloid beta are covered in chapters 4-6. Despite being ultimately unsuccessful, this part provided a deeper understanding of the …

Fine-Mapping Of Human Antibody Specificity In Response To Natural Chlamydia Trachomatis Infection Utilized To Inform Vaccines Against Adhesion Factors, Amanda L. Collar

Biomedical Sciences ETDs

Chlamydia trachomatis (Ct) is the causative pathogen for the most common bacterial sexually transmitted infection worldwide and can cause serious medical consequences in women, including pelvic inflammatory disease, ectopic pregnancy, and infertility. For these reasons, a Ct vaccine is urgently needed, yet, its development remains a significant challenge. One barrier to producing a Ct vaccine is the gap in knowledge of protective immune responses for Ct infection, including the role that antibodies may play. Therefore, I aimed to characterize the human antibody response to natural urogenital Ct infection in women using Deep Sequence-Coupled Biopanning. Further, I leveraged these findings to …

Transcriptomic Analysis Of Liver Indicates Novel Vaccine To Porcine Reproductive And Respiratory Virus Promotes Homeostasis In T-Cell And Inflammatory Immune Responses Compared To A Commercial Vaccine In Pigs, Damarius S. Fleming, Laura C. Miller, Jiuyi Li, Albert Van Geelen, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

One of the largest impediments for commercial swine production is the presence of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), a devastating RNA viral infection that is responsible for over $1 billion in loss in the U.S. annually. The challenge with combating PRRSV is a combination of the effect of an extraordinary rate of mutation, the ability to infect macrophages, and subversion of host immune response through a series of actions leading to both immunomodulation and immune evasion. Currently there are a handful of commercial vaccines on the market that have been shown to be effective against homologous infections, but …

Combinatorial Administration Of Synthetic Tlr4 Agonist Ini-2002 And Novel Mincle Agonist Um-1098 Delivered Via A-Snps Results In Synergistic Il-1Β Production In Human Primary Cells And Enhances Th1 And Th17 Responses In Vivo, Grace D. Jones, Asia Marie Stephanie Riel, Alexander Riffey, Cassandra Buhl

Graduate Student Theses, Dissertations, & Professional Papers

Tuberculosis (TB) kills more people each year than any infectious disease worldwide with recent exception of SARS-CoV-2. Though the Bacille Calmette Guerin (BCG) vaccine confers protection against severe extrapulmonary forms of TB, there is no licensed vaccine for the prevention of pulmonary tuberculosis. The strongest correlate of protection against pulmonary tuberculosis is Th1/Th17 biased cell mediated immunity. Several candidates for TB vaccine adjuvants have shown Th1/Th17 polarizing capacity in clinical trials including Mincle agonist trehalose dibehenate (TDB) and TLR4 agonist monophosphoryl lipid A (MPL). Furthermore, combinatorial administration of MPL and TDB formulated in dimethyldioctadecylammonium (DDA) liposomes has been previously reported …

Investigation Of Histomoniasis Prevention In Poultry, Lesleigh Beer

Graduate Theses and Dissertations

Histomonas meleagridis is the etiological agent of histomoniasis, also commonly known as blackhead disease. This protozoal disease of poultry is detrimental to turkeys with flock mortalities often reaching 80-100%, although other gallinaceous birds are susceptible. Since the voluntary removal of nitarsone in 2015, the poultry industry is suffering with no approved prophylactics, therapeutics, or vaccines for this disease. The objectives of this dissertation were to evaluate multiple methods for prevention or control of histomoniasis, including dietary chemoprophylaxis and vaccination. Specifically, this research evaluated quinine as a chemoprophylactic candidate (Chapter 3) or live-attenuated H. meleagridis as vaccine candidates (Chapter 4) in …

Moraxella Species Associated With Infectious Bovine Keratoconjunctivitis: Detection, Characterization, And Immunity, Matthew M. Hille

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Infectious bovine keratoconjunctivitis (IBK) represents the most common ocular disease of cattle. Moraxella bovis (M. bovis) is the only bacteria proven to cause IBK under experimental conditions. A closely related bacteria, Moraxella bovoculi (M. bovoculi) is cultured from IBK lesions more frequently than M. bovis, and is suspected to cause IBK, although a causal relationship between M. bovoculi and IBK has not been confirmed experimentally. Two distinct genotypes were recently characterized in M. bovoculi based on whole genome sequencing. Genotype 1 M. bovoculi appears to represent a potential pathogen …

Piglet Immunization With A Spike Subunit Vaccine Enhances Disease By Porcine Epidemic Diarrhea Virus, Jieshi Yu, Chithra Sreenivasan, Tirth Uprety, Rongyuan Gao, Chen Huang, Ella J. Lee, Steven Lawson, Julie Nelson, Jane Christopher-Hennings, Radhey S. Kaushik, Eric Nelson, Diego G. Diel, Ben M. Hause, Feng Li, Dan Wang

Maxwell H. Gluck Equine Research Center Faculty Publications

Immunization with an insect cell lysate/baculovirus mixture containing recombinant porcine epidemic diarrhea virus (PEDV) spike protein induced high levels of neutralizing antibodies in both mice and piglets. However, immunization of piglets with this vaccine resulted in enhancement of disease symptoms and virus replication in vaccine recipients exposed to PEDV challenge. Thus, these observations demonstrate a previously unrecognized challenge of PEDV vaccine research, which has important implications for coronavirus vaccine development.

Of Pigs And Men: The Best-Laid Plans For Prevention And Control Of Swine Fevers, Jishu Shi, Lihua Wang, David Scott Mcvey

School of Veterinary and Biomedical Sciences: Faculty Publications

John Steinbeck drew the title of his novel “Of Mice and Men” from a line in a Robert Burns poem “To a mouse”: “The best-laid plans of mice and men/Go often awry.” Unlike John Steinbeck who used the title to mirror the characters who were struggling during the Great Depression to the mouse whose nest was accidentally destroyed by the poet (Burns 1785), we chose this line to emphasize that the best-laid plan can go wrong in infectious disease control and prevention. Here, we will discuss the contributing factors behind the global successes and failures in the prevention and control …

Isotype-Specific Outcomes In Fc Gamma Receptor Targeting Of Pspa Using Fusion Proteins As A Vaccination Strategy Against Streptococcus Pneumoniae Infection, Kari Wiedinger

Seton Hall University Dissertations and Theses (ETDs)

Streptococcus pneumoniae (Spn) remains a considerable threat to public health despite the availability of antibiotics and polysaccharide conjugate vaccines. The lack of mucosal immunity in addition to capsular polysaccharide diversity, has proved to be problematic in developing a universal vaccine against Spn. Targeting antigen to Fc receptors is an attractive way to augment both innate and adaptive immunity against mucosal pathogens, by promoting interactions with activating Fcγ receptors (FcγR) that mediate diverse immunomodulatory functions. The effect of targeting FcγR is highly influenced by the IgG subclass, which bares differential affinities for activating and inhibitory FcγR. In the current study we …

Development Of An Attenuated Zika Virus By Editing The 5’ Untranslated Region, E. Ashley Thompson

Master's Theses

Zika Virus (ZIKV) is a mosquito-transmitted flavivirus that usually causes no symptoms to mild febrile in humans, and it has been regarded as an insignificant pathogen to public health. However, recent outbreaks of ZIKV infection have revealed that ZIKV can cause severe neurological effects in adults, such as Guillain-Barre Syndrome (GBS), and in infants whose mothers acquired the virus during pregnancy, causing Congenital Zika Syndrome (CZS). Currently, no approved vaccine is available and there is a critical need to develop an effective and safe vaccine. While most vaccine developmental strategies target the viral prM-E protein of ZIKV, we aimed to …

Why The Government Shouldn't Pay People To Get Vaccinated Against Covid-19, Ana Santos Rutschman

All Faculty Scholarship

As several pharmaceutical companies approach the Food and Drug Administration (FDA) seeking authorization to bring COVID-19 vaccines to market, concerns about vaccine mistrust cloud the prospects of imminent vaccination efforts across the globe. These concerns have prompted some commentators to suggest that governments may nudge vaccine uptake by paying people to get vaccinated against COVID-19. This post argues that, even if potentially viable, this idea is undesirable against the backdrop of a pandemic marked by the intertwined phenomena of health misinformation and mistrust in public health authorities. Even beyond the context of COVID-19, paying for vaccination is likely to remain …

Haemonchus Contortus Antigen Identification And Use Of Tropomyosin In Ovine Vaccine Development, Brynnan P. Russ

Graduate Theses, Dissertations, and Problem Reports (ETD)

Globally, the small ruminant industry loses hundreds of millions of dollars due to parasitism by the gastrointestinal nematode Haemonchus contortus. This parasite feeds on blood in the host’s abomasum leading to disease including anemia, hypoproteinemia, lethargy, and death. There have been exhaustive efforts to manage this parasite including different management applications, anthelmintic treatment, and now integration of resistance genetics into a flock. Like antibiotics, overuse of anthelmintics has led to resistance of H. contortus to these drugs. Therefore, other methods of control are the main focuses of many research initiatives. St. Croix are a resistant breed of sheep that mount …

Adult Worm Exclusion And Histological Data Of Dogs Repeatedly Infected With The Cestode Echinococcus Multilocularis, Hirokazu Kouguchi, Hidefumi Furuoka, Takao Irie, Jun Matsumoto, Ryo Nakao, Nariaki Nonaka, Yasuyuki Morishima, Kazuhiro Okubo, Kinpei Yagi

Harold W. Manter Laboratory of Parasitology: Library Materials

The data presented in this article are related to a previously published research article titled The timing of worm exclusion in dogs repeatedly infected with the cestode Echinococcus multilocularis (Kouguchi et al. 2016). This data describe a comparison of worm exclusion in the early stage of infection (1 day and 6 days post-infection) between dogs infected for the first time (control group) and dogs repeatedly infected with the parasite 4 times (repeated infection groups). We observed that 6 days post reinfection, the number of adult worms in repeated-infection groups decreased by 88.7% compared with the control group. Histological analysis comparison …

Performance Differences Between Two Groups Of Commercial Pigs Following Experimental Infection With Prrs Virus 1-7-4, Erin Little

Electronic Theses and Dissertations

Porcine reproductive and respiratory syndrome virus (PRRSV) is the costliest swine disease in North America. Vaccines and management alone have not been effective in controlling this disease. Genetic selection for resilience may be a complimentary approach for controlling PRRSV. The objective of this study was to estimate performance differences between two groups of pigs from the same commercial line following infection with PRRSV 1-7-4: 1) pigs sired by boars selected based on a standard index (TN-S), which emphasized feed efficiency and carcass quality; and 2) pigs sired by boars selected based on an experimental index (TN-E), which emphasized feed intake, …

Trypanosoma Cruzi Trypomastigote Glycosylphosphatidylinositol-Anchored Mucins And A Synthetic Alpha-Gal-Containing Neoglycoprotein As Potential Biomarkers And Vaccines For Chagas Disease, Igor Leandro Estevao

Open Access Theses & Dissertations

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a neglected tropical disease that kills or permanently disable thousands of people annually. About 6-8 million people are estimated to be infected worldwide. Although many efforts have been made for the development of an effective immunotherapy, currently there is no vaccine to prevent or treat CD in humans. Despite their toxicity, the two current drugs for CD, benznidazole (BZN) and nifurtimox (NFX), have medium-to-high efficacy in the chronic stage of the disease and could save or improve the lives of thousands of patients. However, negative seroconversion in treated patients, as …

First Results On Survival From A Large Phase 3 Clinical Trial Of An Autologous Dendritic Cell Vaccine In Newly Diagnosed Glioblastoma, Linda M. Liau, Keyoumars Ashkan, David D. Tran, Jian L. Campian, John E. Trusheim, Charles S. Cobbs, Jason A. Heth, Michael Salacz, Sarah Taylor, Stacy D. D'Andre, Fabio M. Iwamoto, Edward J. Dropcho, Yaron A. Moshel, Kevin A. Walter, Clement P. Pillainayagam, Robert Aiken, Rekha Chaudhary, Samuel A. Goldlust, Daniela A Bota, Paul Duic, Jai Grewal, Heinrich Elinzano, Steven A. Toms, Kevin O. Lillehei, Tom Mikkelsen, Tobias Walbert, Steven R. Abram, Andrew J. Brenner, Steven Brem, Matthew G. Ewend, John L. Villano

Internal Medicine Faculty Publications

Background: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax^®-L) to standard therapy for newly diagnosed glioblastoma.

Methods: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS).

Results: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months …