Adenovirus
Adenovirus: a group of viruses that can cause infections in the stomach, intestine, lungs and eyes. Resemble symptoms of the common cold. No effective medications can treat adenovirus infection. Adenovirus infection typically does not cause death or permanent problems. There are more than 40 types of adenoviruses that have been recognized. Adenoviruses for gene therapy and also vaccines are underway.
October 16, 2019 – Adverse events following adenovirus type 4 and type 7 vaccine, live, oral in the Vaccine Adverse Event Reporting System (VAERS), United States, October 2011-July 2018. “During the analytic period, VAERS received 100 reports following adenovirus vaccination; 39 (39%) were classified as serious and of these, 17 (44%) were from the observational study. One death was reported. Males accounted for 72% of reports. Median age of vaccinees was 19 years (range 17–32). The most frequently reported serious AEs were Guillain Barré syndrome (GBS) (n = 12) and anaphylaxis (n = 8); of these, two GBS and all the anaphylaxis reports were reported in the observational study. Reports documented concurrent receipt of multiple other vaccines (95%) and penicillin G (IM Pen G) or other antibiotics (50%).”
February 15, 2019 – Adenovirus based virus-like-vaccines targeting endogenous retroviruses can eliminate growing colorectal cancers in mice “Diverse genomic integrations of viral DNA accumulated in the course of time and today around 8% of the human genome is considered to be endogenous retroviral DNA. … Here we show that even though the vaccine-induced immune responses were deficient in generating antibodies, elevated levels of activated T cells were able to prevent post-vaccine growth of murine colorectal cancer cells, CT26.” Comment: Is this article assuming antibodies are not needed for protection.”
January 1, 2019 – Recombinant Adenovirus Vectored FMDV Vaccines and Uses There of (patent) “Proteins having substantially the same amino acid sequence as the reference molecule but possessing minor amino acid substitutions that do not substantially affect the immunogenicity of the protein are, therefore, within the definition of the reference polypeptide. All of the polypeptides produced by these modifications are included herein. The term “conservative variation” also includes the use of a substituted amino acid in place of an unsubstituted parent amino acid provided that antibodies raised to the substituted polypeptide also immunoreact with the unsubstituted polypeptide.”
July 6, 2018 – Will a Single-Cycle Adenovirus Vaccine Be Effective Against Ebola Virus? “Frequently, the correlate for protective immunity in vaccine trials is virus-specific antibody titer, and, in many cases, the induction of cell-mediated immunity is either not evaluated or is poor. Stimulating a limited cell-mediated response is particularly a concern for nonreplicating viral vaccines, such as subunit or inactivated viral vaccines, that provide a fixed amount of viral antigen and lack the repeated stimulation that is typically required to mount an effective cell-mediated response.”
November 24, 2018 – Adenovirus-Associated Influenza-Like Illness among College Students, Pennsylvania, USA “Although recruits at basic military training are recognized to be at risk for infection with HAdV, less is known about the risk for HAdV in nonmilitary congregate settings. We detected HAdV in a substantial proportion of ILI cases among a convenience sample of young adults at an SHC surveillance site at a large university during the 2016–17 academic year. Understanding the effects of HAdV respiratory illness on college campuses, including severity, missed class time, and occurrence of outbreaks, would be useful in assessing potential control measures in these settings. Comment: Another vaccine heading it’s way to college students:”
October 6, 2017 – Human Adenovirus Surveillance — United States, 2003–2016 “First, NATRS is a passive system that relies on voluntary participation from laboratories, and data might be biased by outbreak investigations and nonrandom sample selection for typing; therefore, types reported might not be representative of the HAdV types circulating nationally or regionally. Second, NATRS collects limited clinical information, restricting the interpretation of trends in HAdV disease associated with circulating types. Third, although quarterly reporting to NATRS is encouraged and allows for retrospective outbreak documentation, not all participating laboratories submit timely data, limiting the ability to detect outbreaks of HAdVs in real-time. Finally, although the number of laboratories with the capacity to test for specific HAdV types and report to NATRS is increasing, the relatively small number of reporters limits the reliability and generalizability of these results.”
June 3, 2016 – Report from the World Health Organization’s Product Development for Vaccines Advisory Committee (PDVAC) meeting, Geneva, 7–9th Sep 2015 (full text) “Novavax’s RSV F-protein based nanoparticle vaccine remains the most advanced candidate, with a Phase III study in pregnant women that started at the end of 2015, following the demonstration in a Phase II study that palivizumab-competing antibody and RSV neutralising antibody were elicited and transferred to infants. In addition, recent preliminary data in the elderly demonstrated efficacy, and a phase III trial has been initiated in that target population (NCT02608502). GSK and J&J also have RSV F vaccines in clinical development that target pregnant women, and MedImmune is developing an RSV F vaccine for use in the elderly. A number of groups have RSV F vaccines in preclinical development, including NIAID. An RSV subunit vaccine containing the SH protein (Immunovax) is also currently being evaluated in adults. A number of live vaccines are in clinical development for active immunisation of infants and young children, including native RSV candidates from which nonessential genes have been deleted, and an adenovirus vector containing the RSV F gene. Passive prophylaxis with a long-half life monoclonal antibody developed by Medimmune is currently being evaluated in a dose-escalation/
May 9, 2015 – Adenovirus-Vectored Vaccine Provides Postexposure Protection to Ebola Virus–Infected Nonhuman Primates “Here, we show that an adjuvanted human adenovirus serotype 5 (Ad5)–vectored vaccine (Ad5–Zaire EBOV glycoprotein) protected 67% (6 of 9) and 25% (1 of 4) of cynomolgus macaques when administered 30 minutes and 24 hours following EBOV challenge, respectively. The treatment also protected 33% of rhesus macaques (1 of 3) when given at 24 hours.” Comment: Clinical trials for HIV was stopped because it was causing HIV, The vector they used Ad5 is the same vector they used in this trial for an Ebola vaccine.
November 28, 2014 – Amplified and Persistent Immune Responses Generated by Single-Cycle Replicating Adenovirus Vaccines ”
November 4, 2014 – How the Current West African Ebola Virus Disease Epidemic Is Altering Views on the Need for Vaccines and Is Galvanizing a Global Effort to Field-Test Leading Candidate Vaccines (full text) “Once sufficient prelicensure safety data are accrued, in future outbreaks the Ebola vaccine could be offered as part of a reactive vaccination clinical trial in which consenting subjects would be given vaccine.”
- Potential conflicts of interest. M. M. L. serves as a member of the Scientific Advisory Working Group to the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID), which has developed two candidate Ebola vaccines slated for clinical trials in West Africa. M. M. L. is also a member of the VRC Board of Scientific Counselors. A. V. H. has a patent on a different chimpanzee adenovirus vaccine vector pending, and a patent on a chimpanzee adenovirus vaccine for malaria issued. He has pioneered the use of chimpanzee adenovirus vectors as vaccines and has been involved in many clinical trials of this technology.
November 2014 – Proof-of-concept for a virus-induced obesity vaccine; vaccination against the obesity agent adenovirus 36 (full text) “Obesity is associated with increased risk of type 2 diabetes, cardiovascular disease, gastrointestinal disorders and several types of cancers. As obesity has become one of the leading health problems in modern society, there is a need to develop effective strategies for weight management. Currently approved antiobesity drugs have only limited efficacy, generally facilitating no more than a 5–10% reduction of body weight, and are often associated with side effects. Thus, there is a major medical need for the development of new antiobesity drugs. In this study, we inactivated purified Ad36 by ultraviolet (UV) irradiation. Mice injected with the inactivated virus were protected from Ad36-induced adiposity and inflammation. Thus, our results provide proof-of-concept for prophylactic vaccination against virus-induced adiposity.”
October 31, 2014 – The Ebola vaccine underdog (full text) “The NewLink vaccine is made from an Ebola gene stitched into a livestock pathogen, vesicular stomatitis virus (VSV). It’s currently unknown whether the vaccine needs 1 million VSV particles per dose or 100 million. Early human studies now under way should answer this question. Abstract
- “Q: What about side effects? The VSV vaccine was used in 2009 to treat a lab worker who had a needlestick injury in Germany. What happened? A: The woman developed a temperature of 38.5°[C]. I don’t think you can have a vaccine that causes high fever in a significant portion of subjects, especially where fever is the first indication of Ebola. But she was given a dose of 5 × 107 [virus particles], based on an extrapolation from monkey studies. We’re hoping that at the lower doses people might have low-grade fevers, but there won’t be high-grade fevers.
- Q: Is there a risk of VSV spreading from vaccinated people and infecting livestock? A: It’s a legitimate concern and we’re looking at ways to evaluate that.
March 11, 2014 – Proof-of-concept for a virus-induced obesity vaccine; vaccination against the obesity agent adenovirus 36 “The control group showed 17% greater body weight and 20% more epididymal fats compared with the vaccinated group. In addition, the vaccinated group had decreased serum levels of pro-inflammatory cytokines, and infiltrated immune cells, especially M1 macrophages, in fat tissue. Therefore, the vaccine candidate for Ad36 was able to protect against Ad36-increased body weight and fat as well as inflammatory states after challenge. These results provide proof-of-concept for prophylactic vaccination against virus-induced adiposity.”
April 2013 – Airway Delivery of an Adenovirus-Based Ebola Virus Vaccine Bypasses Existing Immunity to Homologous Adenovirus in Nonhuman Primates “This study shows that airway vaccination with adenovirus serotype 5-based Ebola virus vaccine can efficiently bypass preexisting immunity to adenovirus serotype 5 and induce protective immune responses, albeit at lower efficacy than that using an intramuscular vaccine delivery route.”
January 2013 – An Adenovirus-Vectored Nasal Vaccine Confers Rapid and Sustained Protection against Anthrax in a Single-Dose Regimen “To mitigate an onslaught from airborne anthrax spores that are maliciously disseminated, it is of paramount importance to develop a rapid-response anthrax vaccine that can be mass administered by nonmedical personnel during a crisis. We report here that intranasal instillation of a nonreplicating adenovirus vector encoding B. anthracis protective antigen could confer rapid and sustained protection against inhalation anthrax in mice in a single-dose regimen in the presence of preexisting adenovirus immunity.”
December 2012 – Incorporation of Antigens into Viral Capsids Augments Immunogenicity of Adeno-Associated Virus Vector-Based Vaccines “Genetic modification of adeno-associated virus (AAV) capsids has previously been exploited to redirect viral tropism. Here we demonstrate that engineering of AAV capsids as scaffolds for antigen display augments antigen-specific immunogenicity.”
November 27, 2012 – Recombinant adeno-associated virus vector for treatment of Alzheimer disease (patent) “A method for treating Alzheimer’s disease in a mammal in need thereof, comprising orally administering to the mammal a DNA vaccine composition, wherein said composition comprises an adeno-associated virus vector encoding a .beta.-amyloid peptide and a signal peptide capable of extracellularly secreting said .beta.-amyloid peptide, in an operative form, wherein said administering results in suppressing formation of an amyloid plaque in the central nervous system and reducing the concentration of TGF-.beta.1 in the blood of the mammal, and wherein administering said composition maintains therapeutic activity for at least 6 months.”
October 30, 2012 – Sequential administration of a replication defective adenovirus vector in vaccination protocols (patent) “Methods for generating immune responses using adenovirus vectors that allow multiple vaccinations with the same adenovirus vector and vaccinations in individuals with preexisting immunity to adenovirus are provided.”
October 2, 2012 – Peptides for active anti-cytokine immunization (patent) “In the case of DNA vaccine administered by systemic or mucosal route, the galenic presentation of the plasmid can be a suspension in a physiological liquid such as physiological PBS (phosphate buffered saline=PBS). The plasmids can be enclosed in biodegradable polymer (PLG, PLA, PCL) microspheres and administered in gastroresistant capsules for ingestion (oral route). The DNA can also be expressed in a bacterial, salmonella-type or viral-type, adenovirus or poxvirus living vector.”
April 17, 2012 – Adenovirus Vaccines Reinstated After Long Absence “In December 1995, Wyeth informed the department that they would require two years for construction and one year for approval of the production line and product by FDA for continued manufacture of the vaccine; the estimated costs ranged from $3M to $5M. In July 1996, Wyeth indicated it preferred to transfer the technology rather than continuing to make the vaccine. Discussions within the department ultimately led to a decision to not fund the Wyeth request, or to take other procurement actions. The existing supply of vaccine was depleted or expired in 1999.””
‘