Vaccine Research

On Wednesday, January 11, 2012, Peter J. Hotez, MD, PhD, gave the Maurice Hilleman Pediatric Grand Rounds lecture at The Children’s Hospital of Philadelphia/University of Pennsylvania. Hotez is an internationally recognized expert on tropical diseases and vaccine development and holds the following positions: Professor of Pediatrics and Molecular Virology & Microbiology and Chief of the Section of Pediatric Tropical Medicine at Baylor College of Medicine; Endowed Chair of Tropical Pediatrics at Texas Children’s Hospital; and President, Sabin Vaccine Institute. More

It’s National Influenza Vaccination Week, and we’re taking a look back to 1918, the time of the “Spanish” influenza pandemic. When the illness emerged, several useful vaccines had already been developed: smallpox, typhoid fever, and rabies, for example. Scientists and physicians tried many different approaches to develop influenza vaccines during the pandemic even though the cause of influenza was not clear. We look at several of them below.

No other epidemic has claimed as many lives as the Spanish influenza epidemic in 1918-1919. Worldwide, at least 40 million people died as this virulent illness swept through city after city (some estimates put total deaths closer to 70 million). Newspaper reports described people dying within hours of first feeling ill. The mortality rate was highest among adults under age 50, who were, for unknown reasons, particularly vulnerable to serious disease resulting from this strain of influenza.

The first reported cases of an unusual influenza appeared in U.S. Army camps in Kansas in early spring 1918. Later that spring, officials reported large numbers of cases from Europe, though this flu did not seem particularly dangerous. However, influenza became more deadly in late summer. Soon waves of infection moved through towns, nations, and continents, overwhelming hospitals and medical personnel. Because of wartime censorship, reports of influenza were not widely distributed, but news from Spain continued to flow. The name Spanish influenza came from the devastating effects of the flu in Spain in autumn 1918. More

The so-called Spanish influenza pandemic of 1918 was one of the worst natural disasters in history. Estimates of total death counts vary, but it is commonly stated that the virus infected about one-third of the world’s population and killed about 50 million – possibly as many as 100 million. Researchers have long been interested in learning more about the virus and what made it so deadly, and genetic analysis has been a large part of that effort. In 2005 the full genome sequence of the virus was published, and research has continued from that point.

The virus behind the 1918 pandemic was an H1N1 strain; in fact, it was the only H1N1 strain to cause a pandemic in the 20th century. (Pandemics that began in China in 1956 and Hong Kong in 1968 were caused by H2N2 and H3N2 strains, respectively.) It was unusually severe, and in an unexpected result for an influenza virus, tended to kill healthy young adults rather than the typical flu victims – the very old and the very young. This contributed to the initial fear when novel H1N1 appeared in 2009, particularly since the number of deaths per age group early in the outbreak skewed heavily toward young adults. More

Two important vaccine meetings were held September 11 and 12 at The College of Physicians of Philadelphia. The September 12 meeting entitled Research Integrity Challenges in Vaccine Development and Distribution for Public Health Emergencies was sponsored by the Department of Health and Human Services, the Office of Research Integrity, Drexel University, University of Pennsylvania Center for Bioethics, and The College of Physicians of Philadelphia. Speakers focused on vaccine development and distribution for biological threats and how the emergency preparedness experiences with A/H1N1 provided lessons that might inform future preparation for similar public health emergencies. More

Human papillomavirus (HPV) is primarily known for its role in causing cervical cancer. Two strains of the virus – strains 16 and 18 – are estimated to be responsible for 70% of cervical cancer cases, leading to about 500,000 new cases and 270,000 deaths worldwide each year.

Both of the HPV vaccines available in the United States have been shown to be effective in preventing cervical infection with strains 16 and 18. The Gardasil quadrivalent vaccine also offers protection against two strains that cause genital warts. But HPV’s role in cancer is not limited to cervical cancer; the virus can also cause oral, anal, and penile cancer. More

Each year, researchers select three influenza strains to include in the seasonal flu vaccine. Because there are so many different strains of the influenza virus, and because it mutates so rapidly, this selection is always a guess—a highly educated one based on global surveillance data, but still a guess.

In some years, the selections turn out to be remarkably accurate. During the 2010-2011 flu season, for example, the three strains selected for the seasonal flu vaccine were a very good match to strains circulating in the wild. In other years, however, researchers haven’t been so lucky. And since immunity to one strain of the flu doesn’t necessarily provide protection against other strains, a poor match between the vaccine strains and the circulating ones may mean an ineffective flu vaccine.

Researchers have long hoped to develop a so-called “universal” flu vaccine: one that could provide protection against all, or at least most, of the many strains of influenza capable of making people sick. If such a vaccine could be developed, the need for a new seasonal shot every year could be a thing of the past. More

Last December, the History of Vaccines blog covered the introduction of MenAfriVac to the African meningitis belt, an area stretching from Senegal to Ethiopia, where epidemic waves of meningitis occur and can last up to three years. In the largest of these epidemic waves in history, meningitis killed more than 25,000 people from 1996 to 1997.

Polysaccharide vaccines are sometimes used to try to control outbreaks after they have begun: so-called “emergency vaccination” efforts designed to keep meningococcal epidemics from spreading further. However, these types of reactive efforts are very expensive and difficult to manage, and polysaccharide vaccines do not induce long-lasting immunity against meningococcal bacteria. (For more about the different types of vaccines, see our article and Types of Vaccines activity.)

Within these African epidemics, between 80 and 85% of cases are caused by a single group of meningococcal bacteria: group A. In 2000, a group of global health leaders gathered together by the World Health Organization (WHO) determined that a meningitis vaccine could be developed specifically for use in Africa: a low-cost vaccine that would focus solely on the Group A bacteria. The Bill & Melinda Gates Foundation provided a ten-year grant for what would become the Meningitis Vaccine Project (MVP). More

We recently interviewed Paul A. Offit, MD, about his experience developing a rotavirus vaccine. His vaccine, known generically as rotavirus oral vaccine (commercially as RotaTeq), has been part of the recommended childhood immunization schedule since 2006. In the interview, Offit discusses an experience with rotavirus disease as a young physician, working with Stanley Plotkin, MD (developer of the rubella vaccine), the long process of creating the rotavirus vaccine, and the relief and pride involved in receiving encouraging safety results from post-licensure monitoring. He also discusses, more generally, how a researcher goes about developing a new vaccine.

Click the picture to see one of the interview segments in The History of Vaccines Gallery. See the entire set of Offit interview segments by searching for “Offit” in The History of Vaccines search box and clicking the Media tab to access all six video clips.

Dr. Offit is Chief of the Division of Infectious Diseases at The Children’s Hospital of Philadelphia. More

A January 5, 2011 report in the British Medical Journal investigates the 1998 paper that first alleged a link between the MMR vaccine and autism. The author, Brian Deer, presents evidence that the paper resulted from research fraud. The History of Vaccines blog looks at the history of the paper and how it has profoundly affected research, public health, and the public perception of vaccines over the last 12 years.

In the wake of a paper published in the Lancet in 1998, vaccination rates in Britain plummeted. The lead author of the paper, Andrew Wakefield, rose to infamy as a result of his claims that the combination measles, mumps and rubella (MMR) vaccine had caused autism in the 12 children in the study, and frightened parents began to delay or completely refuse vaccination for their children, both in Britain and the United States. Since then, outbreaks of previously eliminated diseases have sickened and killed children in both countries. More

Influenza is a challenging disease for vaccine researchers. At any given time, multiple influenza strains are circulating, and immunity against one strain does not necessarily provide protection against others. In addition, influenza A viruses frequently mutate, so that it is difficult to find a "target" within the virus that will remain stable between various strains and mutations. As a result, the current approach for developing flu vaccines is based on observations of the strains most likely to be circulating in the coming flu season. The seasonal flu vaccine contains three inactivated strains of influenza, but typically can't provide protection against other strains.

Now, the results of a recent study in mice suggest that a new approach may be able to provide long-lasting, cross-strain protection against influenza. More