Kading R.C.,Centers for Disease Control and Prevention |
Biggerstaff B.J.,Centers for Disease Control and Prevention |
Young G.,Centers for Disease Control and Prevention |
Young G.,Madison Vaccines |
Komar N.,Centers for Disease Control and Prevention
PLoS ONE | Year: 2014
Serial samples from the same individuals may be required for certain virological studies, however, some small animals cannot easily be blood-sampled. Therefore, we evaluated the use of Culex quinquefasciatus Say and Aedes albopictus Skuse mosquitoes as "biological syringes" to draw blood for virus titer determinations in small vertebrates. Groups of chicks (Gallus gallus), hamsters (Mesocricetus auratus), and house sparrows (Passer domesticus) were experimentally infected with West Nile virus (WNV) or Highlands J virus (HJV). In general, good correlation was seen between mosquito- and syringe-derived blood samples at titers ≥5.0 log10 pfu/mL serum as compared with titers <5.0 log10 pfu/mL serum for chicks, hamsters, and sparrows. Ninety-two percent (24/26) of sparrows with virus titers >105 pfu/mL serum had mosquito- and syringe-derived titers within one log of each other. Sparrow viremia profiles generated from single mosquito blood meals and syringe were not significantly different (p>0.05). This technique is valuable for assessing the roles of small vertebrates in the ecologies of arboviruses, and could be used in applications beyond virology and infectious diseases, when <10 μL of whole blood is required.
Ambuel Y.,Madison Vaccines |
Young G.,Madison Vaccines |
Brewoo J.N.,Madison Vaccines |
Paykel J.,Madison Vaccines |
And 9 more authors.
Frontiers in Immunology | Year: 2014
Dengue viruses (DENVs) cause approximately 390 million cases of DENV infections annually and over 3 billion people worldwide are at risk of infection. No dengue vaccine is currently available nor is there an antiviral therapy for DENV infections. We have developed a tetravalent live-attenuated DENV vaccine tetravalent dengue vaccine (TDV) that consists of a molecularly characterized attenuated DENV-2 strain (TDV-2) and three chimeric viruses containing the pre-membrane and envelope genes of DENV-1, -3, and -4 expressed in the context of the TDV-2 genome. To impact dengue vaccine delivery in endemic areas and immunize travelers, a simple and rapid immunization strategy (RIS) is preferred. We investigated RIS consisting of two full vaccine doses being administered subcutaneously or intradermally on the initial vaccination visit (day 0) at two different anatomical locations with a needle-free disposable syringe jet injection delivery devices (PharmaJet) in non-human primates. This vaccination strategy resulted in efficient priming and induction of neutralizing antibody responses to all four DENV serotypes comparable to those elicited by the traditional prime and boost (2 months later) vaccination schedule. In addition, the vaccine induced CD4+ and CD8+ T cells producing IFN-Γ, IL-2, and TNF-α, and targeting the DENV-2 NS1, NS3, and NS5 proteins. Moreover, vaccine-specific T cells were cross-reactive with the non-structural NS3 and NS5 proteins of DENV-4. When animals were challenged with DENV-2 they were protected with no detectable viremia, and exhibited sterilizing immunity (no increase of neutralizing titers post-challenge). RIS could decrease vaccination visits and provide quick immune response to all four DENV serotypes. This strategy could increase vaccination compliance and would be especially advantageous for travelers into endemic areas. © 2014 Ambuel, Young, Brewoo, Paykel, Weisgrau, Rakasz, Haller, Royals, Huang, Capuano, Stinchcomb, Partidos and Osorio.
News Article | October 27, 2016
MADISON, Wis.--(BUSINESS WIRE)--Madison Vaccines advances prostate cancer vaccines. Expands trial to NJ in addition to WI for vaccine to prolong disease control. Will present data on second vaccine at medical conference in NOV.
Fuchs J.,Madison Vaccines |
Chu H.,Madison Vaccines |
O'Day P.,Madison Vaccines |
Pyles R.,University of Texas Medical Branch |
And 6 more authors.
Vaccine | Year: 2014
Dengue (DEN) is the most important mosquito-borne viral disease, with a major impact on global health and economics, caused by four serologically and distinct viruses termed DENV-1 to DENV-4. Currently, there is no licensed vaccine to prevent DEN. We have developed a live attenuated tetravalent DENV vaccine candidate (TDV) (formally known as DENVax) that has shown promise in preclinical and clinical studies and elicits neutralizing antibody responses to all four DENVs. As these responses are lowest to DENV-4 we have used the AG129 mouse model to investigate the immunogenicity of monovalent TDV-4 or tetravalent TDV vaccines, and their efficacy against lethal DENV-4 challenge. Since the common backbone of TDV is based on an attenuated DENV-2 strain (TDV-2) we also tested the efficacy of TDV-2 against DENV-4 challenge. Single doses of the tetravalent or monovalent vaccines elicited neutralizing antibodies, anti-NS1 antibodies, and cellular responses to both envelope and nonstructural proteins. All vaccinated animals were protected against challenge at 60 days post-immunization, whereas all control animals died. Investigation of DENV-4 viremias post-challenge showed that only the control animals had high viremias on day 3 post-challenge, whereas vaccinated mice had no detectable viremia. Overall, these data highlight the excellent immunogenicity and efficacy profile of our candidate dengue vaccine in AG129 mice. © 2014 Elsevier Ltd.
News Article | November 8, 2016
MADISON, Wis. & NATIONAL HARBOR, Md.--(BUSINESS WIRE)--Madison Vaccines Inc. says early research shows combining its MVI-816 vaccine with a PD-1 inhibitor is safe, and does stimulate an immune response in patients with advanced prostate cancer.
Safrit J.T.,International AIDS Vaccine Initiative |
Fast P.E.,International AIDS Vaccine Initiative |
Gieber L.,International AIDS Vaccine Initiative |
Kuipers H.,International AIDS Vaccine Initiative |
And 2 more authors.
Vaccine | Year: 2016
Human immunodeficiency virus (HIV) is the cause of one of the most lethal pandemics in human history, although in recent years access to highly effective anti-retroviral therapy has provided new hope worldwide. Transmission of HIV by sexual contact, childbirth and injection drug use has been reduced, but 2 million are newly infected each year, and much of the transmission is from people who do not know their status. In addition to known methods, a preventive vaccine is needed to end the pandemic. The extraordinary mutability and genetic diversity of HIV is an enormous challenge, but vaccines are being designed for broad coverage. Computer-aided design of mosaic immunogens, incorporating many epitopes from the entire genome or from conserved regions aim to induce CD8+ T cells to kill virus-infected cells or inhibit virus replication, while trimeric envelope proteins or synthetic mimics aim to induce broadly reactive neutralizing antibodies similar to those cloned from some infected patients. Induction of more potent and durable responses may require new adjuvants or replicating chimeric vectors chimeras that bear HIV genes. Passive or genetic delivery of broadly neutralizing antibodies may provide broad protection and/or lead to insights for vaccine designers. Proof-of-concept trials in non-human primates and in one human efficacy trial have provided scientific clues for a vaccine that could provide broad and durable protection against HIV. The use of vaccines to destroy HIV reservoirs as part of therapy or cure is now also being explored. © 2016 The Authors.
Caine E.A.,University of Wisconsin - Madison |
Fuchs J.,Madison Vaccines |
Das S.C.,Madison Vaccines |
Partidos C.D.,Madison Vaccines |
And 2 more authors.
Viruses | Year: 2015
Hand, foot, and mouth disease (HFMD) has recently emerged as a major public health concern across the Asian-Pacific region. Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are the primary causative agents of HFMD, but other members of the Enterovirus A species, including Coxsackievirus A6 (CVA6), can cause disease. The lack of small animal models for these viruses have hampered the development of a licensed HFMD vaccine or antivirals. We have previously reported on the development of a mouse model for EV71 and demonstrated the protective efficacy of an inactivated EV71 vaccine candidate. Here, mouse-adapted strains of CVA16 and CVA6 were produced by sequential passage of the viruses through mice deficient in interferon (IFN) α/β (A129) and α/βand γ(AG129) receptors. Adapted viruses were capable of infecting 3 week-old A129 (CVA6) and 12 week-old AG129 (CVA16) mice. Accordingly, these models were used in active and passive immunization studies to test the efficacy of a trivalent vaccine candidate containing inactivated EV71, CVA16, and CVA6. Full protection from lethal challenge against EV71 and CVA16 was observed in trivalent vaccinated groups. In contrast, monovalent vaccinated groups with non-homologous challenges failed to cross protect. Protection from CVA6 challenge was accomplished through a passive transfer study involving serum raised against the trivalent vaccine. These animal models will be useful for future studies on HFMD related pathogenesis and the efficacy of vaccine candidates. © 2015 by the authors.
PubMed | University of Wisconsin - Madison and Madison Vaccines
Type: Journal Article | Journal: Viruses | Year: 2015
Hand, foot, and mouth disease (HFMD) has recently emerged as a major public health concern across the Asian-Pacific region. Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are the primary causative agents of HFMD, but other members of the Enterovirus A species, including Coxsackievirus A6 (CVA6), can cause disease. The lack of small animal models for these viruses have hampered the development of a licensed HFMD vaccine or antivirals. We have previously reported on the development of a mouse model for EV71 and demonstrated the protective efficacy of an inactivated EV71 vaccine candidate. Here, mouse-adapted strains of CVA16 and CVA6 were produced by sequential passage of the viruses through mice deficient in interferon (IFN) / (A129) and / and (AG129) receptors. Adapted viruses were capable of infecting 3 week-old A129 (CVA6) and 12 week-old AG129 (CVA16) mice. Accordingly, these models were used in active and passive immunization studies to test the efficacy of a trivalent vaccine candidate containing inactivated EV71, CVA16, and CVA6. Full protection from lethal challenge against EV71 and CVA16 was observed in trivalent vaccinated groups. In contrast, monovalent vaccinated groups with non-homologous challenges failed to cross protect. Protection from CVA6 challenge was accomplished through a passive transfer study involving serum raised against the trivalent vaccine. These animal models will be useful for future studies on HFMD related pathogenesis and the efficacy of vaccine candidates.
News Article | August 28, 2014
Madison Vaccine to be Tested in Combination Prostate Cancer Treatment [Corrected 8/29/14, 8:39 a.m. See below.] Madison Vaccines, a Madison, WI-based startup developing immunotherapies for prostate cancer, will get a chance to see how well its lead vaccine can shrink tumors when teamed up with another drug. The Phase I trial will be led by Madison Vaccines co-founder Doug McNeel, an oncologist and professor of medicine at the University of Wisconsin-Madison. McNeel and a team of university researchers were awarded a $1.5 million grant to conduct the study. The Movember Foundation is providing the funding through the Movember-Prostate Cancer Foundation Challenge Award program. [An earlier version of this article indicated the grant was awarded to the company. We regret the error.] The broader pharmaceutical industry will likely keep an eye on the study, as experts agree that beating prostate cancer will almost certainly require a mix of more than one treatment. The question is figuring out the best recipe. Madison Vaccines (MVI) is creating vaccines from tiny circular bits of DNA called plasmids. The company’s lead DNA vaccine, MVI-816, contains instructions for a protein named prostatic acid phosphatase (PAP), which is made by prostate cells. When injected into the skin, the DNA is taken up by the body’s cells, which use the DNA to make copies of the PAP protein. That protein, in turn, acts as an antigen to stimulate an immune response against PAP. MVI’s lead vaccine, which is entering Phase II trials, has been primarily tested in patients after their prostates have been removed, but before the cancer has spread to the bones or other organs. The idea is to prevent, or at least delay, the onset of metastases and the need for castration by priming the immune system to recognize cancerous cells and kill them. But the trial funded by the $1.5 million grant, which will begin enrolling patients within a year, will attempt to treat patients with metastatic prostate cancer. MVI’s lead vaccine will be combined with an undetermined PD-1 pathway inhibitor drug, which is designed to keep cancer cells from camouflaging themselves. These inhibitor drugs have shown promise against some diseases, like melanoma and some lung cancers, but they haven’t worked well against prostate cancer, said MVI co-founder and CEO Rick Lesniewski. McNeel has conducted pre-clinical research that suggests teaming an inhibitor with MVI’s lead vaccine could more effectively treat prostate cancer, Lesniewski said. In theory, the inhibitor would help reveal the cancer cells, and the vaccine would teach the body’s immune system to knock them out. “We believe this two-pronged immune activation approach, pairing a PD-1 pathway inhibitor with a vaccine, will generate the results we need to have a significant impact on this disease,” McNeel said in a prepared statement. While MVI moves forward with its separate Phase II trial, the new study could speed up commercialization of MVI’s lead vaccine, Lesniewski said. The Phase II trial will take at least two years, partly because MVI will try to demonstrate that the drug delays the spread of cancer—rather than the typical cancer drug test that aims to shrink a tumor in a matter of weeks or months. But because the new Phase I trial will treat patients with tumors that can be measured, it could face a shorter timeline—assuming the two drugs work as the company and its funders envision. “If we were to see tumor responses in this trial, which haven’t been seen with PD-1 alone, that could start to reveal a clinical signal that the two are working synergistically together,” Lesniewski said.