PPD forms Vaccines & Biologics Center of Excellence

PPD, Inc. announced the launch of PPD Vaccines & Biologics Center of Excellence, described as “a first-in-kind comprehensive network of integrated, world-class laboratory services focused specifically on vaccine and biologic drug development.” PPD said the Center significantly expands vaccine testing services PPD acquired from Merck in 2009. “With the industry’s largest collection of commercial vaccine assays and strong immunochemistry, cell culture and cGMP lab operations, PPD is the first CRO to offer the type of laboratory support that has the potential to bring significant efficiencies to the development of vaccines and biologics,” the company said.

Christine Dingivan, M.D., chief medical officer, PPD, commented, “With the industry’s largest collection of commercial vaccine assays and strong immunochemistry, cell culture and cGMP lab operations, PPD is the first CRO to offer the type of laboratory support that has the potential to bring significant efficiencies to the development of vaccines and biologics. The Vaccines & Biologics Center of Excellence provides the high quality scientific support our clients are seeking in a way that allows them to bypass costly capital and resource investments necessary to develop and maintain these capabilities internally.”


H1N1 infection in England: cross-sectional serological study

The Lancet
Mar 27, 2010  Volume 375  Number 9720  Pages 1053 – 1134

Incidence of 2009 pandemic influenza A H1N1 infection in England: a cross-sectional serological study
Elizabeth Miller, Katja Hoschler, Pia Hardelid, Elaine Stanford, Nick Andrews, Maria Zambon

Knowledge of the age-specific prevalence of immunity from, and incidence of infection with, 2009 pandemic influenza A H1N1 virus is essential for modelling the future burden of disease and the effectiveness of interventions such as vaccination.

In this cross-sectional serological survey, we obtained 1403 serum samples taken in 2008 (before the first wave of H1N1 infection) and 1954 serum samples taken in August and September, 2009 (after the first wave of infection) as part of the annual collection for the Health Protection Agency seroepidemiology programme from patients accessing health care in England. Antibody titres were measured by use of haemagglutination inhibition and microneutralisation assays. We calculated the proportion of samples with antibodies to pandemic H1N1 virus in 2008 by age group and compared the proportion of samples with haemagglutination inhibition titre 1:32 or more (deemed a protective response) before the first wave of infection with the proportion after the first wave.

In the baseline serum samples from 2008, haemagglutination inhibition and microneutralisation antibody titres increased significantly with age (F test p<0·0001). The proportion of samples with haemagglutination inhibition titre 1:32 or more ranged from 1·8% (three of 171; 95% CI 0·6—5·0) in children aged 0—4 years to 31·3% (52 of 166; 24·8—38·7) in adults aged 80 years or older. In London and the West Midlands, the difference in the proportion of samples with haemagglutination inhibition titre equal to or above 1:32 between baseline and September, 2009, was 21·3% (95% CI 8·8—40·3) for children younger than 5 years of age, 42·0% (26·3—58·2) for 5—14-year-olds, and 20·6% (1·6—42·4) for 15—24-year-olds, with no difference between baseline and September in older age groups. In other regions, only children younger than 15 years showed a significant increase from baseline (6·3%, 1·8—12·9).

Around one child in every three was infected with 2009 pandemic H1N1 in the first wave of infection in regions with a high incidence, ten times more than estimated from clinical surveillance. Pre-existing antibody in older age groups protects against infection. Children have an important role in transmission of influenza and would be a key target group for vaccination both for their protection and for the protection of others through herd immunity.

National Institute for Health Research Health Technology Assessment Programme.

Global Climate Change and Infectious Diseases

New England Journal of Medicine
Volume 362 — March 25, 2010 — Number 12

Global Climate Change and Infectious Diseases
E. K. Shuman

[Initial article language per NEJM convention]
The 2009 United Nations Climate Change Conference in Copenhagen ended on December 18 without passage of a binding resolution for tackling global climate change. With the debate over U.S. health care reform raging, this event went largely unnoticed by the U.S. health care community. However, climate change will have enormous implications for human health, especially for the burden of vectorborne and waterborne infectious diseases…

Universal Mass Rotavirus Vaccination: Austria

The Pediatric Infectious Disease Journal
April 2010 – Volume 29 – Issue 4

Original Studies
Universal Mass Vaccination Against Rotavirus Gastroenteritis: Impact on Hospitalization Rates in Austrian Children

Paulke-Korinek, Maria; Rendi-Wagner, Pamela; Kundi, Michael; Kronik, Renate; Kollaritsch, Herwig

Background: Since July 2007, rotavirus vaccinations have been subsidized in Austria for all children from the seventh week up to the sixth month of life. Vaccination coverage over the whole period was 72% with an increase to 87% in 2008.

Methods: In a sentinel network including 11 pediatric hospital wards in Austria, data of children up to 15 years of age and hospitalized due to rotavirus gastroenteritis between January 2001 and December 2008 have been collected.

Results: The hospitalization rates of children up to 12 months of age with rotavirus gastroenteritis were 2066 x 10-5 between 2001 and 2006 and decreased to 631 x 10-5 in 2008. For children between 12 and 24 months of age the hospitalization rate decreased from 1822 x 10-5 (2001-2006) to 1456 x 10-5 in 2008. In children aged 2 to less than 5 years, incidence rates were 436 x10-5 (2001-2006) and 461 x 10-5 in 2008. In older children, the hospitalization rates remained unchanged. In the target population for the RV-vaccine, a decrease of hospitalization rates due to rotavirus gastroenteritis of 74% was observed compared to the era before the introduction of the vaccine. The field effectiveness of the vaccine was estimated between 61% and 98%, depending on assumptions about the vaccination status.

Conclusions: Within 18 months, the universal mass vaccination program against rotavirus led to a substantial decrease in the hospitalization rates of the target cohort of the immunization program in Austria.

(C) 2010 Lippincott Williams & Wilkins, Inc.

News: 1918 Virus Matches 2009 H1N1 Strain

26 March 2010  Vol 327, Issue 5973, Pages 1543-1678

News of the Week
Swine Flu Pandemic: What’s Old Is New: 1918 Virus Matches 2009 H1N1 Strain
Jon Cohen

The “novel” H1N1 swine influenza virus that last year caused the first human pandemic in 4 decades has one feature that is hardly novel: Its surface protein, hemagglutinin (HA)—which spikes cells and starts an infection—closely matches the HA in the H1N1 virus responsible for the 1918 pandemic. Separated by 91 years, the two strains of the highly mutable virus ought to be vastly different. This newfound similarity answers many mysteries about the 2009 pandemic, including why it largely spared the elderly. The new findings, reported online this week in Science and Science Translational Medicine, also suggest intriguing explanations for how the 1918 influenza virus has evolved since it swept across the globe in several waves, killing more than 50 million people by the winter of 1919. And the investigators are proposing provocative—some say far-fetched—vaccination strategies to preempt future pandemics. Science Express Index

Published Online March 25, 2010

Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus
Rui Xu,1, Damian C. Ekiert, Jens C. Krause, Rong Hai, James E. Crowe, Jr., Ian A. Wilson

The 2009 H1N1 swine flu is the first influenza pandemic in decades. The crystal structure of the hemagglutinin from the A/California/04/2009 H1N1 virus shows that its antigenic structure, particularly within the Sa antigenic site, is extremely similar to human H1N1 viruses circulating early in the 20th century. The co-crystal structure of the 1918 HA with 2D1, an antibody from a survivor of the 1918 Spanish flu that neutralizes both 1918 and 2009 H1N1 viruses, reveals an epitope that is conserved in both pandemic viruses. Thus, antigenic similarity between the 2009 and 1918-like viruses provides an explanation for the age-related immunity to the current influenza pandemic.

1918 and 2009 Influenza Viruses: Common Features

Science Translational Medicine
24 March 2010 vol 2, issue 24

Research Articles
Cross-Neutralization of 1918 and 2009 Influenza Viruses: Role of Glycans in Viral Evolution and Vaccine Design
Chih-Jen Wei, Jeffrey C. Boyington, Kaifan Dai, Katherine V. Houser, Melissa B. Pearce, Wing-Pui Kong, Zhi-yong Yang, Terrence M. Tumpey, and Gary J. Nabel

Editor’s Abstract
New strains of H1N1 influenza virus have emerged episodically over the last century to cause human pandemics, notably in 1918 and recently in 2009. Pandemic viruses typically evolve into seasonal forms that develop resistance to antibody neutralization, and cross-protection between strains separated by more than 3 years is uncommon. Here, we define the structural basis for cross-neutralization between two temporally distant pandemic influenza viruses—from 1918 and 2009. Vaccination of mice with the 1918 strain protected against subsequent lethal infection by 2009 virus. Both were resistant to antibodies directed against a seasonal influenza, A/New Caledonia/20/1999 (1999 NC), which was insensitive to antisera to the pandemic strains. Pandemic strain–neutralizing antibodies were directed against a subregion of the hemagglutinin (HA) receptor binding domain that is highly conserved between the 1918 and the 2009 viruses. In seasonal strains, this region undergoes amino acid diversification but is shielded from antibody neutralization by two highly conserved glycosylation sites absent in the pandemic strains. Pandemic HA trimers modified by glycosylation at these positions were resistant to neutralizing antibodies to wild-type HA. Yet, antisera generated against the glycosylated HA mutant neutralized it, suggesting that the focus of the immune response can be selectively changed with this modification. Collectively, these findings define critical determinants of H1N1 viral evolution and have implications for vaccine design. Immunization directed to conserved receptor binding domain subregions of pandemic viruses could potentially protect against similar future pandemic viruses, and vaccination with glycosylated 2009 pandemic virus may limit its further spread and transformation into a seasonal influenza.