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The invention pertains to a technique for enhancing the resolution of images in light sheet microscopy by adding additional enhanced depth-of-focus optical arrangements and high numerical aperture objective lenses. The technique employs an arrangement of three objective lenses and a processor for combining captured images. The image composition utilizes the greater resolving power of the third high numerical aperture objective lens by imaging the light sheet and enhanced depth-of-focus arrangement resulting in improved overall resolution of the light sheet system.

This invention is a platform technology that pertains to the advantages of conjugating therapeutics to Evans Blue thus providing long lasting pharmacokinetic profiles by complexing with albumin. Notably, albumin bound therapeutic- or prodrug-Evans Blue conjugates provide a complex with a total molecular size above 60 kDa thus eliminating the risk for renal clearance. Interestingly, since albumin also crosses the blood-brain barrier and since all circulating Evans Blue is bound to albumin, Evans Blue bound therapeutics or prodrugs can also cross the blood-brain barrier.

Zika virus (ZIKV) is a flavivirus transmitted by mosquitos that is strongly linked to neurological complications including Guillain-Barré syndrome, meningoencephalitis, and microcephaly. The association between active ZIKV infection during pregnancy and microcephaly and intrauterine growth retardation in the fetus has been confirmed in murine models of ZIKV infection.

Many members of the Flaviviridae family are emerging and reemerging human pathogens that have caused outbreaks of devastating and often fatal diseases and represent a serious public health problem on a global scale. There is no single attenuation strategy that exists which is sufficient to prepare a safe, efficacious and immunogenic live attenuated virus vaccine that will work universally for Flaviviridae.

An arthropod-borne virus, Zika virus (ZIKV), has recently emerged as a major human pathogen. Associated with complications during perinatal development and Guillain-Barré syndrome in adults, ZIKV raises new challenges for understanding the molecular determinants of flavivirus pathogenesis. This underscores the necessity for the development of a reverse genetic system based on an epidemic ZIKV strain. This technology relates to the generation and characterization in cell cultures of an infectious cDNA clone of ZIKV isolated from the 2015 epidemic in Brazil.

This application claims live attenuated Zika viruses and vaccines, attenuated chimeric Zika viruses and vaccines, and multivalent immunogenic compositions comprising Zika vaccines and vaccines for other flaviviruses. The chimeric Zika viruses claimed include a first nucleotide sequence encoding at least one structural protein from a Zika virus (ZIKV), a second nucleotide sequence encoding at least one nonstructural protein from a first flavivirus, and a third nucleotide sequence of a 3' untranslated region from a second flavivirus.

Inhibiting the ability of HIV-1, the virus that causes AIDS, to infect cells is one approach to both prevention and treatment of HIV. Scientists at the NIAID Vaccine Research Center have isolated and characterized neutralizing antibodies (VRC01, 02, 03, and 07) that bind to the CD4 binding site of HIV-1 envelope glycoprotein gp120. These human monoclonal antibodies can potentially be used as a therapeutic to: (1) treat an HIV infection, (2) decrease and prevent HIV-transmission from mother to infant, and (3) be effectively combined with anti-retroviral drug therapy.

The National Institute of Allergy and Infectious Diseases has invented three chlamydial vaccine technologies, which have shown promising preclinical efficacy. Chlamydia trachomatis infection is the most common sexually transmitted bacterial infection. If left untreated, chlamydia infection can lead to pelvic inflammatory disease and infertility. Chlamydia is also the leading cause of preventable blindness in the world. Despite increased surveillance, prevalence continues to increase, and the need to develop an effective chlamydial vaccine remains.

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