It's flu season again, which always focuses public attention on the reliablity and availability of the nation's vaccine supply.
It's flu season again, which always focuses public attention on the reliability and availability of the nation's vaccine supply. The Centers for Disease Control and Prevention (CDC) expect to have more vaccine available this season-166 million dosages versus 157 million in the 2010-2011 season-and have launched a major campaign to vaccinate more healthcare workers and pregnant women. Last year about 42% of Americans were immunized, more than usual, but still far below the 80% goal set by the federal government. While the vaccine community won plaudits for responding quickly to the 2009-2010 flu pandemic, the World Health Organization (WHO) came under fire for slow distribution of vaccines in poor countries, as well as charges that it hyped the danger of the epidemic to boost drug company sales. A blue-ribbon panel rejected those charges, but the debate reveals the highly-charged political environment surrounding immunization programs.
Vaccines have even made it into the Republican presidential race, as Texas Governor Rick Perry publicly disavowed his earlier backing of the HPV (human papillomavirus) vaccine for all young girls. Perry signed an executive order in 2007 mandating that all sixth-grade girls in Texas receive Merck's Gardasil vaccine to prevent cervical cancer. Now candidate Perry says he made a mistake-an about-face that reflects concerns raised by social conservatives about vaccine mandates overall, and specifically about endorsing a preventive for a sexually-transmitted disease.
Other important developments this year brought good news to vaccine producers and advocates. The Supreme Court ruled in February that manufacturers can't be sued in state court for injuries supposedly caused by their products. The case, Bruesewitz v. Wyeth (Feb. 22, 2011), should discourage plaintiffs from trying to circumvent the protections created by the 1986 National Childhood Vaccine Injury Act, which provides compensation from the industry-funded Vaccine Injury Compensation Program (VCIP) to patients claiming injury from vaccines.
Perennial concerns about vaccine safety prompted a recent in-depth analysis by the Institute of Medicine (IOM), which documents in great detail that vaccines cause few adverse effects and have no links to serious health conditions. The expert committee's August report on "Adverse Effects of Vaccines" [ http://www.iom.edu/vaccineadverseeffects] finds little scientific evidence of health problems caused by 8 widely used vaccines, and further discredits links between the MMR (measles, mumps, rubella) vaccine and autism. The report confirms the huge health benefits of vaccines and should encourage more parents to vaccinate their children; it also will help the Department of Health and Human Services (HHS) decide vaccine compensation cases under the VCIP program.
Despite lingering safety issues, vaccine research and new product development is expanding, generating optimism for new discoveries that will guard against AIDS, cancer, and multiple infectious diseases. Led by the Bill & Melinda Gates Foundation, which has committed more than $10 billion to support vaccine innovation, donor nations are boosting support for global vaccine R&D. Researchers anticipate that a dozen new vaccines may be rolled out in the next decade against diseases such as typhoid, malaria, and dengue fever.
The journal Health Affairs discussed strategies for achieving Gates' "Decade of Vaccines" in a special June 2011 issue that explores new vaccines in the pipeline along with new models for financing and paying for vaccine development and delivery. The promise is that investing more in immunization science and expanding vaccine distribution globally will reduce healthcare costs, promote economic activity and save the lives of more than 6 million children through 2020.
Pharmaceutical manufacturers now regard vaccines as a potential source of steady revenue, if not blockbuster profits. The world market for preventive vaccines exceeded $20 billion in 2009 and grew to nearly $30 billion in 2010. Projections call for 10% annual growth over the next 5 years due to new product introductions and broader utilization. Expanded global production of seasonal flu vaccine is setting the pace: by 2015, WHO predicts that some 37 vaccine makers will be able to produce 1.7 billion doses of influenza vaccine, enough to handle any pandemic. Merck, GlaxoSmithKline, Sanofi Pasteur, Pfizer, and Novartis dominate the market and continue to invest in the field.
A main target of vaccine research is the development of new treatments for third-world diseases. A new meningitis A vaccine has been distributed to more than 19 million people in West Africa, providing a model for collaboration to produce and distribute a vaccine that costs less than 50 cents per dose. Sanofi Pasteur is testing the first vaccine for dengue fever, and researchers have begun early clinical trials for a new vaccine for tuberculosis, with initial results expected next year. Vaccines are under development for schistosomiasis, hookworm, rabies, chikungunya virus (CHIKV), and Ebola virus.
Several groups are working on malaria vaccine projects, according to a June 2011 study describing dozens of vaccine candidates in development to prevent this disease. The most advanced is Glaxo's RTS,S vaccine candidate, now in phase 3 studies in Africa under the auspices of the PATH Malaria Vaccine Initiative. In addition, the Infectious Diseases Research Institute (IDRI) is collaborating with the US Agency for International Development and the Walter Reed Army Institute of Research to develop an anti-malarial vaccine that combines new antigens.
Despite numerous failures in developing an AIDS vaccine, scientists remain optimistic that success is possible. Researchers point to advances in understanding the complexities of an AIDS vaccine and are developing new vectors, delivery technologies, adjuvants, and immune assays to address these challenges. For example, the International AIDS Vaccine Initiative (IAVI), Scripps Research Institute, and several biotech companies recently reported the isolation of novel antibodies capable of neutralizing a broad spectrum of variants of HIV. Researchers were encouraged that this could provide new targets for the design of vaccine candidates that can elicit similar antibodies to protect against the virus.
New cancer vaccines are on everyone's wish list, encouraged by success in developing HPV vaccines for cervical cancer and the prostate cancer treatment, Provenge (Dendreon). A recent announcement from the Mayo Clinic in Rochester, Minn., cites plans for phase 1 clinical trials for new vaccines to prevent the recurrence of ovarian and breast cancer.
Bioterrorism threats also are spurring vaccine development. Last year, the Biomedical Advanced Research and Development Authority (BARDA), an agency within the Office of the Assistant Secretary for Preparedness and Response in HHS, awarded some $50 million to organizations seeking to reduce the time and cost of testing new medical countermeasures. Projects aim to increase the shelf life of influenza vaccine stockpiles for future use in a pandemic and to develop adjuvant formulations to enhance influenza vaccine immunogenicity and cross-protection to new viral strains.
PRICES AND ACCESS
Vaccine development, though, generates tension between making R&D profitable enough to encourage private sector investment, and seeking sufficiently low prices to make products available to poor nations. While public health officials admit that the most cost-effective vaccine is one that's free, the stated goal is to provide emerging markets with vaccines that cost less than $5 per dose. At a June meeting in London to secure donor funding for the Global Alliance for Vaccines and Immunization (GAVI), India-based manufacturers promised a record low $1.75 per dose price for pentavalent vaccines that protect against five diseases-diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae type b (HIB). Glaxo and Merck reduced rates on rotavirus and HPV vaccines, and other leading manufacturers announced similar moves. GAVI will have the funds to purchase these more affordable products, as the Gates Foundation and major donor nations pledged $4.3 billion in June to support its international immunization program.
Even in the United States, too-high prices appear to limit vaccine utilization. Sales have been sluggish for Dendreon's Provenge despite a positive national coverage decision from Medicare that has prompted insurer coverage. But full treatment costs more than $100,000 due to a complex regimen that involves manipulation of a patient's own immune cells. Physicians appear reluctant to prescribe Provenge due to tight insurer utilization requirements, high copays, and limited evidence of effectiveness.
Price may be a factor in slow vaccination rates for the HPV vaccine. CDC analysis for 2010 shows that more teens received vaccines to protect against meningitis (63%) and tetanus-diphtheria-pertussis (69%), but only 49% of young girls received 1 dose of the HPV vaccine, and only 32% received the full 3-dose regimen.
Although cost issues may limit utilization of some vaccines, adult immunization has gained support from health reform legislation. The Affordable Care Act requires insurers to cover all recommended vaccines for adults, with no copays or deductibles, as part of efforts to expand preventive care. The policy applies now to new group and individual health plans, but is expected to affect all coverage over time.
Ms Wechsler is a Washington-based reporter specializing in federal and state healthcare issues.