Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques.

Article added to library!

PubChase

'); var ntfc_preview = ''; $.post('/api/v1/get_notifications', function(r) { var ntfc_read_pending = 0; var ntfc_pending = 0; $.each(r.notifications.pending, function(index, ntfc_object) { ntfc_read_pending++; ntfc_pending++; if (ntfc_read_pending

' + ntfc_object.full_name +'' + ntfc_object.time + '

' + ntfc_object.description +'

'; }) if (ntfc_read_pending

' + ntfc_object.full_name +'' + ntfc_object.time + '

' + ntfc_object.description +'

'; }) $('.notification-block .dropdown-menu').html(ntfc_preview); $('.notification-block .dropdown-menu').append('

'); if (ntfc_pending > 0) { $('.notification-count').text(ntfc_pending).show(); } else { $('.notification-count').hide(); } } else { $('.notification-block .dropdown-menu').html(ntfc_preview); $('.notification-block .dropdown-menu').append('

'); if (ntfc_pending > 0) { $('.notification-count').text(ntfc_pending).show(); } else { $('.notification-count').hide(); } } if (ntfc_read_pending == 0) { $('.notification-block .dropdown-menu').html('

You don\'t have any notifications

'); $('.notification-count').hide(); } data = {'nid' : '', 'ntid' : 1}; $.post('/api/v1/notification_action', data, function(r) { if (r.request == 'OK') { $('.notification-count').hide(); } }); }, "json"); }); $('.search-save-box').on({ click : function(e) { e.preventDefault(); var search_attr = $(this).attr('rel').split(','); var p = search_attr[1]; var tf = search_attr[0]; window.location = '/search?tf='+tf+'&jc='+jc+'&keywords='+$(this).html()+'&s='+$('#sort_order').val()+'&p='+p; } }, '.search-name'); $( "#keywords_main, #keywords_mobile" ).focus(function(e) { show_saved_searches(e, $(this)); }); $(window).resize(function () { if ($('.search-save-box').is(':visible')) { if ($('#keywords_main').is(':visible')) var left_search_save = $('#keywords_main').offset().left; if ($('#keywords_mobile').is(':visible')) var left_search_save = $('#keywords_mobile').offset().left; $('.search-save-box').css('left',left_search_save); } }); $('.search-save-box').on({ click : function(e) { e.preventDefault(); delete_saved_search($(this)); } }, '.search-name-close'); $('.search-save-box, #keywords_main, #keywords_mobile').click(function(e) { e.stopPropagation(); }); $(document).click(function(e) { $('.search-save-box').hide(); }); $( "#keywords_main, #keywords_mobile" ).autocomplete({ source: function( request, response ) { // data contains the JSON object textStatus contains the status: success, error, etc $.post('/api/v1/searches', {'key' : request.term}, function(data, textStatus) { response(data); }, "json") }, select: function (event, ui) { var reportname = ui.item.value; var thelinks = '/search?tf='+$('#time_frame').val()+'&jc='+jc+'&keywords='+reportname+'&s='+$('#sort_order').val()+'&p='+$('#people_cluster').val(); } }); $('.search-go').click(function(e) { e.preventDefault(); window.location = get_search_url(); }); $('.logout').click(function(e) { e.preventDefault(); }); $('.header_keywords, .home_page_keywords').on('keydown', function(e) { if (e.keyCode == 13) { window.location = get_search_url(); } $('.search-save-box').hide(); }); $('.seemore').click(function(e){ e.stopImmediatePropagation(); }); });

Add to Library

Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques.

Sep 08, 2015
Vaccines

Borggren M, Vinner L, Andresen BS, Grevstad B, Repits J, Melchers M, Elvang TL, Sanders RW, Martinon F, Dereuddre-Bosquet N, Bowles EJ, Stewart-Jones G, Biswas P, Scarlatti G, Jansson M, Heyndrickx L, Grand RL, Fomsgaard A

HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

Add Public PDF

Upload my PDF

Downloading PDF to your library...

ADD A TAG 64 chars max

Make private

APPLIED TAGS

Uploading PDF...

PDF uploading

Delete tag:

The link you entered does not seem to be valid

Please make sure the link points to nature.com contains a valid shared_access_token