In: Plos neglected tropical diseases, 2011, vol. 5, no. 6, p. e1188
Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and,...
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In: Plos one, 2011, vol. 6, no. 3, p. e18207
Neutralizing antibodies have been shown to protect macaques against SHIV challenge. However, genetically diverse HIV-1 clades have evolved, and a key question left unanswered is whether neutralizing antibodies can confer cross-clade protection in vivo. The novel human monoclonal antibody HGN194 was isolated from an individual infected with an HIV-1 clade AG recombinant circulating recombinant...
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In: Plos one, 2011, vol. 6, no. 2, p. e16819
Attenuated poxviruses are safe and capable of expressing foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the...
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In: Plos pathogens, 2010, vol. 6, no. 11, p. e1001195
The human monoclonal antibody (mAb) HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1) of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 A° resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a...
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In: The Journal of clinical investigation, 2010, vol. 120, no. 5, p. 1663-1673
The target of neutralizing antibodies that protect against influenza virus infection is the viral protein HA. Genetic and antigenic variation in HA has been used to classify influenza viruses into subtypes (H1–H16). The neutralizing antibody response to influenza virus is thought to be specific for a few antigenically related isolates within a given subtype. However, while heterosubtypic...
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In: Plos one, 2010, vol. 5, no. 1, p. e8805
Background The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. Methods and Findings We immortalized IgG+ memory B cells from individuals infected with...
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In: Proceedings of the national academy of sciences of the United States of America, 2014, vol. 111, no. 50, p. 17965-17970
The use of neutralizing antibodies to identify the most effective antigen has been proposed as a strategy to design vaccines capable of eliciting protective B-cell immunity. In this study, we analyzed the human antibody response to cytomegalovirus (human cytomegalovirus, HCMV) infection and found that antibodies to glycoprotein (g)B, a surface glycoprotein that has been developed as a HCMV...
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In: Proceedings of the national academy of sciences of the United States of America, 2018, vol. 115, no. 40, p. 10112-10117
Viruses with membranes fuse them with cellular membranes, to transfer their genomes into cells at the beginning of infection. For Influenza virus, the membrane glycoprotein involved in fusion is the hemagglutinin (HA), the 3D structure of which is known from X-ray crystallographic studies. The soluble ectodomain fragments used in these studies lacked the “membrane anchor” portion of the...
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In: Journal of virology, 2014, vol. 88, no. 16, p. 8826-8842
GII.4 noroviruses (NoVs) are the primary cause of epidemic viral acute gastroenteritis. One primary obstacle to successful NoV vaccination is the extensive degree of antigenic diversity among strains. The major capsid protein of GII.4 strains is evolving rapidly, resulting in the emergence of new strains with altered blockade epitopes. In addition to characterizing these evolving blockade...
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In: Journal of virology, 2014, vol. 88, no. 13, p. 7244–7255
Genogroup II, genotype 4 (GII.4) noroviruses are known to rapidly evolve, with the emergence of a new primary strain every 2 to 4 years as herd immunity to the previously circulating strain is overcome. Because viral genetic diversity is higher in chronic than in acute infection, chronically infected immunocompromised people have been hypothesized to be a potential source for new epidemic...
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