Flu vaccination: optimizing delivery

jorgemata — Wed, 24 Sep 2008 04:21:44 -0700

Description

A new approach to improving vaccine supplies in the event of an influenza pandemic is reported online in Mucosal Immunology (http://www.nature.com/mi) this week. The study compares delivery methods of the current vaccine in an animal model and shows that a lower dose delivered to the site of infection, gives better protection against influenza than the normal dose as it is currently delivered. One of the most serious challenges facing human health today is preparing for the next influenza pandemic. Influenza is a major global health issue; in the USA alone influenza infections are associated with an average of 36,000 deaths and 114,000 hospitalisations each year. Mucosal surfaces are linked by an integrated immune system, and protection at mucosal surfaces may be best induced by vaccination at these same sites. Despite this, the vast majorities of approved vaccines are delivered by injection and induce predominantly systemic immunity, even when targeting mucosal pathogens. Australian researchers used a sheep model to test whether immunization at the site of influenza infection, directly in to the lung could improve protection. They found that compared to the currently available vaccine, significantly lower doses of vaccine delivered directly to the lung resulted in better protection against subsequent influenza infection. This finding may have significant implications in the event of a pandemic when vaccine supplies may not meet demand. Abstract: Using a large animal model, we evaluated whether delivery of influenza vaccine via its mucosal site of infection could improve vaccine effectiveness. Unexpectedly, pulmonary immunization with extremely low antigen doses (0.04 ug influenza) induced serum antibody levels equivalent to those resulting from a current human vaccine equivalent (15 ug unadjuvanted influenza, subcutaneously) and vastly superior lung mucosal antibodies. Induction of this potent response following lung vaccination was dependent on addition of ISCOMATRIX adjuvant and deep lung delivery. Functional antibody activity, marked by hemagglutination inhibition, was only present in the lungs of animals that received adjuvanted vaccine via the lungs, suggesting this approach could potentially translate to improved protection. The 375-fold reduction in antigen dose and improved mucosal antibody responses, compared to the current vaccine, suggests that mucosal delivery via the pulmonary route may be particularly relevant in the event of an influenza pandemic, when vaccine supplies are unlikely to meet demand.

Source

Pulmonary delivery of ISCOMATRIX influenza vaccine induces both systemic and mucosal immunity with antigen dose sparing. JLK Wee 1, J-PY Scheerlinck 1, KJ Snibson 1, S Edwards 2, M Pearse 2, C Quinn2 and P Sutton 1. doi 10.1038/mi2008.59

1 Centre for Animal Biotechnology, School of Veterinary Science, University of Melbourne, Melbourne, Australia
2 Research and Development, CSL Limited, Parkville, Australia

1918 Flu: immunity lasts 90 years

jorgemata — Mon, 18 Aug 2008 22:53:24 -0700

Description

Thinking of future pandemics, we got good news from Nature (http://www.nature.com/nature): Antibodies isolated from survivors of the 1918 pandemic influenza virus can protect mice from lethal infection, according to recent research. The finding proves that the immune system in these individuals still 'remembers' the virus nearly 90 years after the initial infection.

US-based researchers found that all 32 individuals tested, born in or before 1915, had antibodies that recognised the 1918 strain of the flu virus. Several of the individuals also had circulating B cells that were still produced these specific antibodies. Importantly, the antibodies were still functional and were able to protect mice from experimental infection with the 1918 viral strain.

The team went on to identify the area on the virus where the antibodies bound to stop infection. The authors suggest that these antibodies could act as useful therapeutics, should another virus similar to the 1918 flu strain ever emerge.

Abstract (citations omitted):

Investigation of the human antibody response to influenza virus infection has been largely limited to serology, with relatively little analysis at the molecular level. The 1918 H1N1 influenza virus pandemic was the most severe of the modern era. Recent work has recovered the gene sequences of this unusual strain, so that the 1918 pandemic virus could be reconstituted to display its unique virulence phenotypes. However, little is known about adaptive immunity to this virus. We took advantage of the 1918 virus sequencing and the resultant production of recombinant 1918 haemagglutinin (HA) protein antigen to characterize at the clonal level neutralizing antibodies induced by natural exposure of survivors to the 1918 pandemic virus. Here we show that of the 32 individuals tested that were born in or before 1915, each showed seroreactivity with the 1918 virus, nearly 90 years after the pandemic. Seven of the eight donor samples tested had circulating B cells that secreted antibodies that bound the 1918 HA. We isolated B cells from subjects and generated five monoclonal antibodies that showed potent neutralizing activity against 1918 virus from three separate donors. These antibodies also cross-reacted with the genetically similar HA of a 1930 swine H1N1 influenza strain, but did not cross-react with HAs of more contemporary human influenza viruses. The antibody genes had an unusually high degree of somatic mutation. The antibodies bound to the 1918 HA protein with high affinity, had exceptional virus-neutralizing potency and protected mice from lethal infection. Isolation of viruses that escaped inhibition suggested that the antibodies recognize classical antigenic sites on the HA surface. Thus, these studies demonstrate that survivors of the 1918 influenza pandemic possess highly functional, virus-neutralizing antibodies to this uniquely virulent virus, and that humans can sustain circulating B memory cells to viruses for many decades after exposure—well into the tenth decade of life.

Source

Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Xiaocong Yu1, Tshidi Tsibane2, Patricia A. McGraw1, Frances S. House1, Christopher J. Keefer1, Mark D. Hicar1, Terrence M. Tumpey3, Claudia Pappas2,3, Lucy A. Perrone3, Osvaldo Martinez2, James Stevens3,4, Ian A. Wilson4, Patricia V. Aguilar2, Eric L. Altschuler5, Christopher F. Basler2 & James E. Crowe Jr1. Nature, Aug 17, 2008, doi 10.1038/nature07231

1 Departments of Pediatrics and ofMicrobiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
2 Department ofMicrobiology, Mount Sinai School of Medicine, New York
3 Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia
4 Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California
5 Department of Physical Medicine and Rehabilitation, University of Medicine & Dentistry of New Jersey, Newark, New Jersey