Beaverton, OR, United States

Najit Technologies, Inc.
Beaverton, OR, United States
Time filter
Source Type

Amanna I.J.,Najit Technologies, Inc. | Slifka M.K.,Oregon Health And Science University
Virology | Year: 2011

Vaccines play a vital role in protecting the host against infectious disease. The most effective licensed vaccines elicit long-term antigen-specific antibody responses by plasma cells in addition to the development of persisting T cell and B cell memory. The relative contributions of these different immune cell subsets are context-dependent and vary depending on the attributes of the vaccine (i.e., live/attenuated, inactivated, and subunit) as well as the biology of the pathogen in question. For relatively simple vaccines against bacterial antigens (e.g., tetanus toxin) or invariant viruses, the immunological correlates of protection are well-characterized. For more complex vaccines against viruses, especially those that mutate or cause latent infections, it is more difficult to define the specific correlates of immunity. This often requires observational/natural history studies, clinical trials, or experimental evaluation in relevant animal models in order for immunological correlates to be determined or extrapolated. In this review, we will discuss the relative contributions of virus-specific T cell and B cell responses to vaccine-mediated protection against disease. © 2010 Elsevier Inc.

Amanna I.J.,Najit Technologies, Inc. | Slifka M.K.,Oregon Health And Science University
Immunological Reviews | Year: 2010

Humoral immunity following vaccination or infection is mainly derived from two types of cells: memory B cells and plasma cells. Memory B cells do not actively secrete antibody but instead maintain their immunoglobulin in the membrane-bound form that serves as the antigen-specific B-cell receptor. In contrast, plasma cells are terminally differentiated cells that no longer express surface-bound immunoglobulin but continuously secrete antibody without requiring further antigenic stimulation. Pre-existing serum or mucosal antibody elicited by plasma cells (or other intermediate antibody-secreting cells) represents the first line of defense against reinfection and is critical for protection against many microbial diseases. However, the mechanisms involved with maintaining long-term antibody production are not fully understood. Here, we examine several models of long-term humoral immunity and present a new model, described as the 'Imprinted Lifespan' model of plasma cell longevity. The foundation of this model is that plasma cells are imprinted with a predetermined lifespan based on the magnitude of B-cell signaling that occurs during the induction of an antigen-specific humoral immune response. This represents a testable hypothesis and may explain why some antigen-specific antibody responses fade over time whereas others are maintained essentially for life. © 2010 John Wiley & Sons A/S.

Dubois M.E.,Najit Technologies, Inc. | Hammarlund E.,Oregon Health And Science University | Slifka M.K.,Oregon Health And Science University
Vector-Borne and Zoonotic Diseases | Year: 2012

Although smallpox has been eradicated, other diseases caused by virulent orthopoxviruses such as monkeypox virus (MPV) remain endemic in remote areas of western and central sub-Saharan Africa, and represent a potential biothreat due to international travel and/or inadvertent exposure. Unfortunately, extensive antigenic cross-reactivity among orthopoxviruses presents a challenge to serological diagnosis. We previously reported a 20mer peptide-based ELISA that identified recent MPV infection with >90% sensitivity and >90% specificity. However, the sensitivity of this approach was not determined with samples obtained at later time points after antibody titers had declined from their peak levels. To improve assay sensitivity for detecting MPV-specific antibodies at later time points, we compared diagnostic 20mer peptides to 30mer peptides. In addition, optimal 30mer peptides were tested in combination or after conjugating selected peptides to a carrier protein (bovine serum albumin) to further improve assay performance. An optimized combination of four unconjugated 30mer peptides provided 100% sensitivity for detecting MPV infection at 2-6 months post-infection, 45% sensitivity for detecting MPV infection at >2 years post-infection, and 99% specificity. However, an optimized combination of two peptide conjugates provided 100% sensitivity for detecting MPV infection at 2-6 months post-infection, 90% sensitivity for detecting MPV infection at >2 years post-infection, and 97% specificity. Peptide-based ELISA tests provide a relatively simple approach for serological detection of MPV infection. Moreover, the systematic approach used here to optimize diagnostic peptide reagents is applicable to developing improved diagnostics to a broad range of other viruses, and may be particularly useful for distinguishing between closely-related viruses within the same genus or family. © Copyright 2012, Mary Ann Liebert, Inc. 2012.

Slifka M.K.,Oregon Health And Science University | Amanna I.,Najit Technologies, Inc.
Vaccine | Year: 2014

Vaccines represent one of the most compelling examples of how biomedical research has improved society by saving lives and dramatically reducing the burden of infectious disease. Despite the importance of vaccinology, we are still in the early stages of understanding how the best vaccines work and how we can achieve better protective efficacy through improved vaccine design. Most successful vaccines have been developed empirically, but recent advances in immunology are beginning to shed new light on the mechanisms of vaccine-mediated protection and development of long-term immunity. Although natural infection will often elicit lifelong immunity, almost all current vaccines require booster vaccination in order to achieve durable protective humoral immune responses, regardless of whether the vaccine is based on infection with replicating live-attenuated vaccine strains of the specific pathogen or whether they are derived from immunization with inactivated, non-replicating vaccines or subunit vaccines. The form of the vaccine antigen (e.g., soluble or particulate/aggregate) appears to play an important role in determining immunogenicity and the interactions between dendritic cells, B cells and T cells in the germinal center are likely to dictate the magnitude and duration of protective immunity. By learning how to optimize these interactions, we may be able to elicit more effective and long-lived immunity with fewer vaccinations. © 2014 Elsevier Ltd.

Amanna I.J.,Najit Technologies, Inc. | Slifka M.K.,Oregon Health And Science University
Expert Review of Vaccines | Year: 2014

West Nile virus (WNV) is a mosquito-borne flavivirus that has become endemic in the United States. From 1999-2012, there have been 37088 reported cases of WNV and 1549 deaths, resulting in a 4.2% case-fatality rate. Despite development of effective WNV vaccines for horses, there is no vaccine to prevent human WNV infection. Several vaccines have been tested in preclinical studies and to date there have been eight clinical trials, with promising results in terms of safety and induction of antiviral immunity. Although mass vaccination is unlikely to be cost effective, implementation of a targeted vaccine program may be feasible if a safe and effective vaccine can be brought to market. Further evaluation of new and advanced vaccine candidates is strongly encouraged. © 2014 Informa UK, Ltd.

Amanna I.J.,Najit Technologies, Inc. | Raue H.-P.,Oregon Health And Science University | Slifka M.K.,Oregon Health And Science University
Nature Medicine | Year: 2012

Safe and effective vaccines are crucial for maintaining public health and reducing the global burden of infectious disease. Here we introduce a new vaccine platform that uses hydrogen peroxide (H 2O 2) to inactivate viruses for vaccine production. H 2O 2 rapidly inactivates both RNA and DNA viruses with minimal damage to antigenic structure or immunogenicity and is a highly effective method when compared with conventional vaccine inactivation approaches such as formaldehyde or β-propiolactone. Mice immunized with H 2O 2-inactivated lymphocytic choriomeningitis virus (LCMV) generated cytolytic, multifunctional virus-specific CD8 + T cells that conferred protection against chronic LCMV infection. Likewise, mice vaccinated with H 2O 2-inactivated vaccinia virus or H 2O 2-inactivated West Nile virus showed high virus-specific neutralizing antibody titers and were fully protected against lethal challenge. Together, these studies demonstrate that H 2O 2-based vaccines are highly immunogenic, provide protection against a range of viral pathogens in mice and represent a promising new approach to future vaccine development. © 2012 Nature America, Inc. All rights reserved.

Amanna I.J.,Najit Technologies, Inc.
Open Longevity Science | Year: 2012

With advances in global health care, ageing populations are expected to grow worldwide throughout the 21 st century. Increased lifespan is a testament to modern medical and social practices, but also presents a growing challenge to a system with limited resources. Elderly populations present specific concerns related to preventative health practices, es-pecially vaccination. Although the power of vaccination is unquestionable in controlling infectious disease, immunosenescence can lead to reduced immune responses following immunization in the elderly, and increased morbidity and mortality. Further complicating this issue, some vaccines themselves may pose a substantial safety risk in the elderly when compared to younger counterparts. Though any health care intervention must balance risk and reward, safety and immunogenicity are often poorly characterized in older populations. This review explores several domestic and travel vaccines, examining what is known concerning efficacy and safety in the elderly, and considers future alternatives. © Ian J. Amanna.

Najit Technologies, Inc. | Date: 2011-04-05

Vaccines for infectious disease.

Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: STTR | Phase: Phase I | Award Amount: 318.59K | Year: 2016

DESCRIPTION provided by applicant Peptide conjugated phosphorodiamidate morpholino oligomers PPMO are single stranded nucleic acid analogs able to modulate gene expression through steric blocking of complementary RNA PPMO are composed of two components an antisense morpholino oligomer cargo covalently conjugated to a cell penetrating delivery peptide PPMO are completely nuclease resistant water soluble and enter cells without assistance These characteristics represent distinct advantages over other antisense technologies PPMO have shown considerable potential against a wide range of clinical targets including several genetic disorders and numerous viral pathogens However the challenge of intracellular endosomal trapping of PPMO is hampering continued clinical development of this class of antisense therapeutics requiring increased doses of PPMO to achieve clinical efficacy and narrowing the therapeutic window for this promising technology The primary objective of this project is to improve the PPMO therapeutic window through the novel combination of an established cell penetrating peptide with endosome disruptive viral fusion peptide motifs We hypothesize that this will enhance intracellular release thus improving the access of the antisense cargo to its RNA targets within the cytosol of cells As a model system to validate this innovative delivery approach we will assess in vitro efficacy using our previously established dengue virus model Dengue virus is a complex human pathogen currently causing a major global public health problem yet despite the acute need no licensed antiviral to treat dengue virus infections is currently available Through this application we have assembled a multidisciplinary team of researchers with unique expertise in nucleic acid delivery technologies Dr Moulton Oregon State University as well as an industry partner Dr Amanna Naj t Technologies Inc each team with andgt years of experience in early stage antiviral clinical development By significantly improving the delivery and activity of the PPMO platform this project is expected not only to enhance the utility of PPMO as a therapeutic class but also to provide a novel strategy for addressing dengue virus infections in humans At the conclusion of this project we anticipate a novel and improved PPMO platform that can be applied to a wide range of clinical targets PUBLIC HEALTH RELEVANCE Peptide conjugated morpholino oligomers PPMO are completely nuclease resistant DNA analogs that enter cells readily and represent an important delivery system for antisense agents However this therapeutic potential is hampered by limited bioavailability primarily due to endosomal trapping We propose to develop novel combinations of viral fusion and cell penetrating peptides to enhance endosomal release of the antisense component of PPMO using dengue virus as a clinically relevant proof of concept target This project will not only develop a PPMO inhibitor against an important human pathogen but will also represent a major advance in the development of this significant therapeutic platform

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 2.99M | Year: 2011

DESCRIPTION (provided by applicant): Yellow fever virus (YFV) was at one time endemic in the United States and represents a mosquito-borne emerging/re-emerging human pathogen that causes up to 20% mortality. The current live attenuated YFV vaccine was developed in 1936 and following the development of a virus seed lot system, it has not been modified or otherwise improved in over 50 years. According to the CDC, this vaccine causes 47 severe adverse events (defined as resulting in hospitalization, long-termdisability, or death) per million vaccinations. More recent reports indicate that vaccine-associated neurological disease occurs at an approximate rate of 1 case per 10,000 vaccinations. YFV vaccination of infants lt 9 months of age has been contraindicated since the 1960's due to high rates of vaccine-associated encephalitis in this age group. The overall (all ages) mortality rate following YFV vaccination is estimated at 1 to 2 deaths per million doses. More recently, YFV vaccination has been found to cause severe viscerotropic disease in a substantial number of patients gt60 years of age (an incidence rate of approximately 1:50,000 doses administered) and these cases result in approximately 50% mortality. This indicates that YFV vaccination is not only contraindicated in infants, but is also not recommended in the elderly due to the increased risk of severe and life-threatening disease. Increased monitoring efforts have also documented several cases of vaccine-related fatalities in young, otherwise healthyadults with no known pre-existing immune deficiencies. There is currently no alternative to live YFV vaccination. In this proposal, we will prepare an inactivated YFV vaccine under GMP conditions and perform the necessary safety, potency, and stability studies required for a future IND submission to the FDA. This vaccine is based on proprietary new technology used to develop inactivated vaccine formulations that can be used to immunize vulnerable populations such as infants and the elderly, in addition toother healthy populations. Preliminary data is provided demonstrating that an H2O2-YFV vaccine is feasible to manufacture, highly immunogenic, and provides full protective immunity against lethal viscerotropic yellow fever. In this project, we will prepareclinical grade vaccine under cGMP conditions, perform in vitro and in vivo safety/toxicity tests, and determine vaccine potency and long-term stability. The successful completion of these objectives will result in cGMP-grade vaccine material suitable forfuture initiation of a Phase I clinical trial. PUBLIC HEALTH RELEVANCE: In this Phase II proposal, we provide strong preliminary data from our Phase I application demonstrating the antigenicity, immunogenicity, and protective efficacy of a proprietary new vaccine platform that can be used to develop a safer and highly effective YFV vaccine.

Loading Najit Technologies, Inc. collaborators
Loading Najit Technologies, Inc. collaborators