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This invention is a microscopy device and system for multi-photon microscopy utilizing multi-view nonlinear optical imaging. Nonlinear optical imaging remains the premier technique for deep-tissue imaging in which typically a multi photon arrangement may be used to illuminate and excite a sample. However, the penetration depth, signal-to-noise ratio, and resolution of this technique is ultimately limited by scattering. The present system addresses these issues by sequential excitation of a sample through three or more objective lenses oriented at different axes intersecting the sample.

Influenza virus is a major public health concern, causing up to 500,000 deaths annually. The current strategy of reformulating vaccines annually against dominant circulating strains leads to variable protective efficacy and is unlikely to protect against novel influenza viruses with pandemic potential. Thus, there is a great need for a vaccine that provides “universal” protection against influenza viruses.

Hermansky-Pudlak Syndrome type-1 (HPS-1) is a rare genetic disorder that affects around 1 in 500,000 people worldwide and 1 in 1,800 Puerto Ricans. Patients with HPS-1 display oculocutaneous albinism, bleeding due to platelet abnormality, and pulmonary fibrosis. Those that develop pulmonary fibrosis often succumb and live no more than a decade after early onset of breathing problems.

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.

Loa loa is a filarial nematode estimated to infect 3-13 million people in Central and Western Africa. In parts of Africa, mass administration of ivermectin is common for onchocerciasis and lymphatic filariasis control. However, some individuals infected with Loa loa microfilariae in high densities are known to experience post-ivermectin severe adverse events, such as encephalopathy, coma, or even death. Therefore, diagnostic tools that can accurately identify and differentiate Loa loa microfilariae from other filarial infections are needed.

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.

Ebola virus infection can lead to severe hemorrhagic fever, known as Ebola virus disease (EVD), which is often fatal. The Zaire species of Ebola virus (EBOV) was responsible for the largest Ebola outbreak in history, which occurred in 2014. Scientists at the NIAID Vaccine Research Center have developed a human monoclonal neutralizing antibody, mAb114 for treatment and prevention of EBOV infection. Because there are very few treatments available to treat or prevent EBOV infection, there is a great need to develop effective pre- and post- exposure therapeutics before another outbreak occurs.

Due to the disorganized nature of blood vessels that run through tumors, chemotherapeutic agents often fail to penetrate tumors and kill cancer cells at the tumor’s center. This can lead to ineffective chemotherapeutic treatments, because tumors can quickly grow back if the entire tumor is not destroyed. NIH researchers have developed a therapeutic agent that solves this problem facing current chemotherapy treatments.