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NIAID, IAVI, Emergent, and Scripps have developed two recombinant adenovirus type 4 (Ad4) vector-based vaccine candidates. These replicating Ad4 vector-based candidates have shown improved activity against tier 2 HIV-1 isolates in experimental animals. Tier 2 isolates are among the most prevalent in infected populations. The two candidates, Ad4-Env150KN and Ad4-Env145NFL, incorporate novel design features based on Ad4-EnvC150 (1086c). Specifically, the truncation of the cytoplasmic tail of Env increases cell surface expression and has resulted in improved antigenicity from both candidates.

Interferons (IFNs) are a family of cytokines that function in response to an immune challenge such as a viral or bacterial infection. Type I IFNs are produced by immune cells (predominantly monocytes and dendritic cells) as well as fibroblasts and signal through a specific cell surface receptor complex (IFNAR) that consist of IFNAR1 and IFNAR2 chains. Type-I IFNs exert several common effects including antiviral, antiproliferative, and immunomodulatory activities. However, Type I IFNs also have pro-inflammatory effects, especially in the presence of TNF-a.

This CDC developed Limiting-Antigen avidity Enzyme Immunoassay (LAg-avidity-EIA) provides an easy way to measure increasing binding strength (avidity) of HIV antibodies as part of maturation HIV antibodies after seroconversion, providing a method to distinguish early-stage from long-term HIV-1 infection. Surveillance of HIV-1 provides information on prevalence rates of the disease, but determination of new infection rates (HIV-1 incidence) is difficult to deduce. Longitudinal follow up is expensive and can be biased.

Rabies virus (RABV) infection leads to fatal encephalitis—inflammation of the brain—if left untreated. Millions of people survive RABV infection each year due to timely administration of post-exposure treatment, however, nearly 60,000 people die from rabies each year according to the World Health Organization. Obstacles to timely treatment for RABV infection include the high cost and burdensome storage requirements (i.e., refrigeration) of current post-exposure treatments (i.e., rabies immunoglobulin (RIG)).

CDC and collaborating researchers have developed a new monoclonal antibody that recognizes canine IgG (likely IgG4 subclass). This anti-dog IgG reagent could be used to detect antibody reactions to a variety of antigens and has potential use in a wide variety of diagnostic or research applications.

According to the World Health Organization (WHO), rabies causes greater than 59,000 deaths every year in over 150 countries as of 2017. A rapid and reliable diagnostic test for rabies is critical for prophylaxis considerations in humans bitten by animals as well as for basic surveillance and animal rabies control programs. The World Organization of Animal Health (OIE) and WHO Expert Committee on Rabies recently approved the direct rapid immunohistochemical test (DRIT) for rabies diagnostics.

NIAID has produced recombinant adenovirus type 4 (Ad4), SARS-CoV-2 spike, vectors for administration to humans. These recombinant vaccines permit rapid development of high levels of neutralizing antibodies to SARS-CoV-2 in experimental animals. This vaccine is designed to improve the durability of the immune response by inducing mucosal and systemic immunity. Further, this system should be incredibly simple and efficient when producing vaccine at scale. This technology is available for licensing for commercial development in accordance with 35 U.S.C.

Flaviviruses such as Zika virus, dengue virus, West Nile virus, yellow fever virus, and Japanese encephalitis virus cause widespread illness and death throughout the world. Typically, flaviviruses get transmitted through the bite of infected mosquitoes and ticks.

Simian T-cell lymphotropic viruses (STLV) are nonhuman primate retroviruses closely related to the human T-lymphotropic virus (HTLV). Types I, II, and III of HTLV have been found in humans and are believed to have originated from cross-species transmission of STLV from infected nonhuman primates. The HTLV viruses are known to cause leukemia, lymphoma, and neurological disorders.

Zika virus (ZIKV) is a flavivirus primarily transmitted by infected Aedes mosquitoes. Infection with ZIKV during pregnancy can affect the fetus causing microcephaly, neurological complications, and other birth defects. Adults are also at a heightened risk of developing Guillain-Barre syndrome and other neurological disorders. In response to the 2015-2016 Zika outbreak, CDC scientists developed a recombinant vaccine candidate as well as reagents and methods to detect ZIKV infection. The recombinant vaccine candidate utilizes adenovirus vector expressed viral envelope proteins.