There is no (or only incomplete) protection from recurrent infection even against the very same S. aureus strain that cause the after primary infection when all the \u2018right\u2019 organism-specific antibodies should be in place.<\/p>\n
Some\u00a0data suggest a role for antibodies as colonized individuals have \u2018milder\u2019 infections than non-colonized patients. \u00a0However, one could argue that this is a rather soft quantitative finding reminiscent of the logic in favor of pneumococcal serum therapy in the days before we had effective antibiotics.<\/p>\n
Importantly, patients with agammaglobulinemia provide the strongest evidence that humoral immunity is not central to the defense against\u00a0\u00a0S. aureus.\u00a0 These patients rarely suffer from S. aureus infections or bacteremia despite having severe recurrent bacterial infections caused by S. pneumoniae, H. influenzae type B, S. pyogenes and P. aeruginosa. [1] By contrast, patients with isolated T-cell deficiencies often battle with invasive S. aureus infections.<\/p>\n
Taken together, it seems that vaccines that trigger just an IgG response are less likely to succeed than those that also stimulate opsonization, upregulate T-cells and activate\u00a0cellular immunity.\u00a0 Hence, the case for new adjuvanted vaccines in order to mobilize both arms of the immune system.[2]<\/p>\n
A recent article brings another hypothesis to the fore.\u00a0 Spaulding et al. tested various antibody preparations against S. aureus virulence factors in a rabbit pneumonia model and found \u2013 quite surprisingly \u2013 that antibodies against circulating virulence factors were protective, while antibodies against bacterial cell surface antigens were actually harmful.[3]<\/p>\n
Is this the explanation why previous vaccine approaches failed?\u00a0 Is this the end of MSCRAMMs [4] as vaccine targets?\u00a0 It seems \u00a0the last word has not been spoken.\u00a0 There are just too many \u201cunknowns\u201d of the Rumsfeld kind as we extrapolate animal data to the human situation. [5]\u00a0 Or, to quote an FDA source: \u201cEverything cures cancer in the mouse\u201d.[6]\u00a0 By extension, let\u2019s include rabbits.<\/p>\n
References:<\/strong><\/p>\n [1] J. Winkelstein. Agammaglobulinemia.\u00a0 2014 http:\/\/www.uptodate.com\/contents\/agammaglobulinemia?source=search_result&search=agammaglobulinemia&selectedTitle=1~53 Several reasons have been proposed as explanations why so many\u00a0S. aureus vaccines\u00a0have failed in clinical trials.\u00a0 Clearly, the organism has a battery of virulence factors which may require a multipronged approach and\u00a0neutralizing just a single mechanism with a specific mAb may not suffice.<\/p>\n","protected":false},"author":1,"featured_media":860,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[227,18],"tags":[386,381,387,384,380,379,383,388,197,301,382,257,385],"class_list":["post-671","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-recent_literature","category-the_viewpoint","tag-adjuvant-vaccine","tag-agammaglobulinemia","tag-cellular-immunity","tag-failed-clinical-trials","tag-h-influenzae","tag-mab","tag-mscramm","tag-opsonization","tag-p-aeruginosa","tag-s-aureus","tag-staphyloccoccal-vaccine","tag-vaccine","tag-virulence-factors"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/06\/MRSA-3-e1410312596956.jpg?fit=240%2C73&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-aP","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":577,"url":"https:\/\/allphasepharma.com\/dir\/2014\/07\/11\/577\/bacterial-vaccine-targets\/","url_meta":{"origin":671,"position":0},"title":"Bacterial Vaccine Targets","author":"Harald","date":"July 11, 2014","format":false,"excerpt":"A recent publication [1] from the team which brought us the Meningococcal B vaccine is of interest from the perspective of vaccine development strategy and feasibility.\u00a0 Appropriately, tuberculosis (TB) leads the list of important bacterial targets for vaccine research. 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\n[2] Bagnoli. Inferring reasons for the failure of Staphylococcus aureus vaccines in clinical trials. Front. Cell. Infect. Microbiol.\u00a0 2012; 2: 1
\n[3] Spaulding. Vaccination against S. aureus pneumonia.\u00a0 JID 2014; 209: 1955
\n[4] MSCRAMM = Microbial Surface Components Recognizing Adhesive Matrix Molecules
\n[5] http:\/\/en.wikipedia.org\/wiki\/There_are_known_knowns
\n[6] McQuinn. \u00a0Oncology Drug Development.\u00a0 A reviewers personal observations.\u00a0 http:\/\/www.toxicology.org\/isot\/rc\/NorCal\/docs\/2010Spring\/2010_1BOncologyDrugDevelop.pdf<\/p>\n","protected":false},"excerpt":{"rendered":"