https:\/\/www.the-scientist.com\/dengue-infection-impairs-immune-defense-against-zika-31055<\/p>\n
A memory B cell response to Zika virus in dengue-infected patients produced antibodies that were poorly neutralizing in vitro and instead enhanced infection.<\/p>\n
\u201cIt\u2019s an important paper,\u201d says Davide Robbiani<\/a>, who studies cross-reactivity in antibodies for dengue and Zika virus at Rockefeller University, but was not involved in the current study. \u201cIt broadens our knowledge of the antibody responses to these viruses and informs how vaccines should be designed.\u201d<\/p>\n At the structural level, Zika virus shows substantial similarities to dengue, another mosquito-borne flavivirus that is endemic to many of the regions now at risk from Zika (see map), and research has shown that antibodies from dengue-infected patients are broadly cross-reactive with Zika virus in vitro.<\/p>\n In particular, Zika shares substantial portions of the viral envelope protein, or E protein, with dengue\u2019s four serotypes (DENV1, 2, 3, and 4). This same protein is currently being explored for vaccine development.<\/p>\n \u201cMost Zika infections are occurring in people that have pre-existing dengue-specific antibodies, many of which, based on previous studies, you would think would cross-react with Zika,\u201d says Laura Walker<\/a>, the associate director of antibody-discovery company Adimab. \u201cWhat we asked was, well, what is the immune response in donors that have these pre-existing antibodies?\u201d<\/p>\n For the current study, Walker and colleagues recruited three recently infected Zika patients living in a region of Colombia where dengue virus is endemic. Preliminary blood tests for the presence of antibodies revealed that all three volunteers had previously been exposed to dengue. The team also took blood samples from a Zika-infected donor in the U.S. who showed no signs of previous dengue infection.<\/p>\n The researchers then measured B cell populations and isolated and characterized hundreds of antibodies from the blood samples of the four donors. They found that the US patient\u2019s blood showed evidence of a small B cell response and the presence of antibodies with low affinity for Zika\u2014a typical feature of early immune reactions to a novel virus.<\/p>\n But the Colombian patients\u2019 blood showed a much larger B cell response, plus antibodies that were broadly cross-reactive with both Zika and dengue\u2014a result likely attributable to a phenomenon, observed in other viruses such as influenza, known as original antigenic sin (OAS).<\/p>\n \u201cOriginal antigenic sin refers to the propensity of the immune system to preferentially utilize immune memory,\u201d Walker explains. In this case, instead of producing novel and potentially more-specific antibodies for Zika virus, the immune system relies on memory B cells from previous dengue infections to launch an immediate immune response\u2014albeit one that\u2019s potentially less effective against new infections.<\/p>\n In line with previous research, the team found that these cross-reactive antibodies were poorly neutralizing and in fact enhanced Zika infection in vitro. This latter result could be due to antibody-dependent enhancement (ADE) that has already been implicated in dengue and Zika infections in mouse models.<\/p>\n In this scenario, \u201cwhen you have a dengue antibody that\u2019s bound to virus, but it\u2019s not neutralizing the virus . . . it can facilitate the interaction of the virus with the [target cell],\u201d Walker explains. However, she adds, ADE has not yet been shown to play a role in Zika infection in humans.<\/p>\n The study\u2019s findings help make the case that Zika vaccine development should focus on portions of the E protein that do not show substantial overlap with that of dengue virus, in order to avoid triggering the memory B cell response in dengue-exposed patients.<\/p>\n \u201cIf you give a vaccine [based on the full-length E protein] to donors that have been exposed to dengue . . . it\u2019s likely that their early immune response might be composed of mostly these antibodies that are poorly neutralizing,\u201d says Walker. \u201cThat\u2019s not good news in terms of protection.\u201d And because potential Zika vaccines are not generally being tested on dengue-exposed patients, \u201cif there is going to be an issue, we might not even see it in clinical trials,\u201d she says.<\/p>\n \u201cThe data is very pertinent for the vaccine efforts for Zika,\u201d says Jean Lim<\/a>, a virologist at the Icahn School of Medicine at Mount Sinai in New York City who recently demonstrated<\/a> ADE occurring in a mouse model of concurrent dengue and Zika infection. While ADE for Zika has yet to be shown in humans, she notes, the results suggest that although \u201ca Zika vaccine may be safe in areas where dengue does not circulate currently, the efficacy of a vaccine administered in dengue-endemic regions would be vastly different.\u201d<\/p>\n Encouragingly, Walker\u2019s team found that when they followed up with the dengue-infected Zika patients five months later, only about 50 percent of the Zika-attacking antibodies were of the cross-reactive, poorly neutralizing variety. \u201cThe other 50 percent, to our surprise, were antibodies that were actually Zika-specific,\u201d Walker says. \u201cThey didn\u2019t recognize any of the serotypes of dengue, and most of them were potently neutralizing. . . . So the original antigenic sin antibodies didn\u2019t just take over.\u201d<\/p>\n Her group is now studying a class of these Zika-neutralizing antibodies that they were unable to identify in the current study. \u201cWe\u2019re collaborating with a group doing structural studies trying to identify where these antibodies are binding,\u201d says Walker. This work, she hopes, \u201ccould reveal new targets for rational vaccine design.\u201d<\/p>\n T.F. Rogers et al., \u201cZika virus activates de novo and cross-reactive memory B cell responses in dengue-experienced donors,\u201d Science Immunology<\/em>, 2:eaan6809, 2017.<\/strong><\/p>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":" https:\/\/www.the-scientist.com\/dengue-infection-impairs-immune-defense-against-zika-31055 A memory B cell response to Zika virus in dengue-infected patients produced antibodies that were poorly neutralizing in vitro and instead enhanced infection. Written byCatherine Offord Previous exposure to dengue virus could dampen a patient\u2019s immune response to Zika, and potentiallyeven aid infection, according to recent work carried out by US researchers. In a […]<\/p>\n","protected":false},"author":121,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"categories":[1],"tags":[],"class_list":["post-1368","post","type-post","status-publish","format-standard","hentry","category-press-2"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/posts\/1368","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/users\/121"}],"replies":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/comments?post=1368"}],"version-history":[{"count":3,"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/posts\/1368\/revisions"}],"predecessor-version":[{"id":1392,"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/posts\/1368\/revisions\/1392"}],"wp:attachment":[{"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/media?parent=1368"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/categories?post=1368"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/tags?post=1368"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}