FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2997431145> ?p ?o ?g. }

• W2997431145 abstract "Abstract HIV-1 vaccine development aims to elicit broadly neutralizing antibodies (bnAbs) against diverse viral strains. In some HIV-1 infected individuals, bnAbs evolve from precursor antibodies through affinity maturation. To induce bnAbs, a vaccine must mediate a similar process of antibody maturation. One way to test vaccination strategies is to immunize mouse models that express human bnAb precursors. Such immunization experiments can assess whether the vaccine can convert precursor antibody into bnAb. A major problem with such mouse models is that bnAb expression often hinders B cell development in the bone marrow. Such developmental blocks may be attributed to unusual properties of bnAb variable regions, such as poly-reactivity and long antigen-binding loops, which are often under negative selection during primary B cell development. To address this problem, we devised a method to circumvent B cell developmental block by expressing bnAbs conditionally in mature B cells. We validated this method by expressing the unmutated common ancestor (UCA) of the human VRC26 bnAb in transgenic mice. Constitutive expression of combined immunoglobulin heavy and light chains of VRC26UCA led to developmental arrest of B cell progenitors in the bone marrow; poly-reactivity of VRC26UCA and poor pairing of VRC26UCA IgH chain with mouse surrogate light chain may contribute to the phenotype. The conditional expression strategy circumvented this developmental impediment, allowing the VRC26UCA to be expressed in mature peripheral B cells. This method should be generally applicable for expressing other antibodies that are under negative selection during B cell development. Significance statement Mouse models can provide fast and cost-effective systems to test HIV-1 vaccine candidates at the pre-clinical stage. To serve this purpose, mouse models are engineered to express the precursors of human bnAbs against diverse HIV-1 strains. Immunization of such mouse models can evaluate the ability of vaccines to mature the precursor antibodies into bnAbs. However, due to unusual properties of bnAbs, mouse models expressing their precursors often have B cell developmental defects. In this study, we devised and validated a strategy to address this problem. This method could also facilitate the expression of other clinically relevant antibodies in mature B cells in transgenic mice; immunization of such mice could be used to generate novel antibodies with desirable properties." @default.
• W2997431145 created "2020-01-10" @default.
• W2997431145 creator A5032598117 @default.
• W2997431145 creator A5033821931 @default.
• W2997431145 creator A5043082145 @default.
• W2997431145 creator A5049261327 @default.
• W2997431145 creator A5051827275 @default.
• W2997431145 creator A5057722534 @default.
• W2997431145 creator A5059302130 @default.
• W2997431145 creator A5063858919 @default.
• W2997431145 creator A5064049296 @default.
• W2997431145 creator A5068104219 @default.
• W2997431145 creator A5071541212 @default.
• W2997431145 creator A5074240743 @default.
• W2997431145 creator A5077707028 @default.
• W2997431145 creator A5085079361 @default.
• W2997431145 creator A5086699118 @default.
• W2997431145 date "2020-01-03" @default.
• W2997431145 modified "2023-09-24" @default.
• W2997431145 title "Conditional Antibody Expression to Avoid Central B Cell Deletion in a Humanized HIV-1 Vaccine Mouse Models" @default.
• W2997431145 cites W136540884 @default.
• W2997431145 cites W1482425583 @default.
• W2997431145 cites W1892803210 @default.
• W2997431145 cites W1893222585 @default.
• W2997431145 cites W1964895771 @default.
• W2997431145 cites W1966889718 @default.
• W2997431145 cites W1966949480 @default.
• W2997431145 cites W1968757041 @default.
• W2997431145 cites W1976275655 @default.
• W2997431145 cites W1979552897 @default.
• W2997431145 cites W1980193047 @default.
• W2997431145 cites W1981525542 @default.
• W2997431145 cites W1982905137 @default.
• W2997431145 cites W1984684498 @default.
• W2997431145 cites W1987541812 @default.
• W2997431145 cites W1996418577 @default.
• W2997431145 cites W2003577929 @default.
• W2997431145 cites W2003893279 @default.
• W2997431145 cites W2008073080 @default.
• W2997431145 cites W2010959676 @default.
• W2997431145 cites W2014334082 @default.
• W2997431145 cites W2016208323 @default.
• W2997431145 cites W2016822118 @default.
• W2997431145 cites W2024303560 @default.
• W2997431145 cites W2032192541 @default.
• W2997431145 cites W2039919570 @default.
• W2997431145 cites W2050772088 @default.
• W2997431145 cites W2056807976 @default.
• W2997431145 cites W2061410538 @default.
• W2997431145 cites W2064421628 @default.
• W2997431145 cites W2078702573 @default.
• W2997431145 cites W2082818240 @default.
• W2997431145 cites W2085377023 @default.
• W2997431145 cites W2092033381 @default.
• W2997431145 cites W2097594050 @default.
• W2997431145 cites W2098497060 @default.
• W2997431145 cites W2101868807 @default.
• W2997431145 cites W2112545544 @default.
• W2997431145 cites W2113367824 @default.
• W2997431145 cites W2130844037 @default.
• W2997431145 cites W2132773138 @default.
• W2997431145 cites W2134544592 @default.
• W2997431145 cites W2135843106 @default.
• W2997431145 cites W2136489732 @default.
• W2997431145 cites W2139978152 @default.
• W2997431145 cites W2141326900 @default.
• W2997431145 cites W2142132827 @default.
• W2997431145 cites W2166317148 @default.
• W2997431145 cites W2234996734 @default.
• W2997431145 cites W2294858472 @default.
• W2997431145 cites W2320044375 @default.
• W2997431145 cites W2381153372 @default.
• W2997431145 cites W2514256437 @default.
• W2997431145 cites W2581429053 @default.
• W2997431145 cites W2581538613 @default.
• W2997431145 cites W2582343367 @default.
• W2997431145 cites W2783812192 @default.
• W2997431145 cites W2883732505 @default.
• W2997431145 cites W2984500766 @default.
• W2997431145 cites W4239202012 @default.
• W2997431145 doi "https://doi.org/10.1101/2020.01.03.894279" @default.
• W2997431145 hasPublicationYear "2020" @default.
• W2997431145 type Work @default.
• W2997431145 sameAs 2997431145 @default.
• W2997431145 citedByCount "0" @default.
• W2997431145 crossrefType "posted-content" @default.
• W2997431145 hasAuthorship W2997431145A5032598117 @default.
• W2997431145 hasAuthorship W2997431145A5033821931 @default.
• W2997431145 hasAuthorship W2997431145A5043082145 @default.
• W2997431145 hasAuthorship W2997431145A5049261327 @default.
• W2997431145 hasAuthorship W2997431145A5051827275 @default.
• W2997431145 hasAuthorship W2997431145A5057722534 @default.
• W2997431145 hasAuthorship W2997431145A5059302130 @default.
• W2997431145 hasAuthorship W2997431145A5063858919 @default.
• W2997431145 hasAuthorship W2997431145A5064049296 @default.
• W2997431145 hasAuthorship W2997431145A5068104219 @default.
• W2997431145 hasAuthorship W2997431145A5071541212 @default.
• W2997431145 hasAuthorship W2997431145A5074240743 @default.
• W2997431145 hasAuthorship W2997431145A5077707028 @default.
• W2997431145 hasAuthorship W2997431145A5085079361 @default.

• next