Global health leaders issue call to action for vaccines in next decade
Intensified research and development, advocacy, increased financing and increased communication about the benefits of vaccines are being advocated by health officials as the best way to usher in a new era of vaccines.
Orin Levine, PhD, of Johns Hopkins Bloomberg School of Public Health, told Infectious Diseases in Children that vaccines are currently saving millions of lives, and funding sources, such as those committed to the Global Alliance for Vaccines and Immunization (GAVI) in mid-June, are steps in the right direction. But more work is needed, according to Levine and others.
As many as 6.4 million lives could be saved during the next 10 years with additional funding, according to Richard Moxon, MA, FRS, FMedSci, of the University of Oxford in the United Kingdom. Moxon said vaccines for tuberculosis, AIDS and malaria are sorely needed, as well as vaccines for about 17 other illnesses, including tropical diseases, respiratory illnesses and gastrointestinal illnesses.
Levine and Moxon both wrote papers recently as part of a series published in The Lancet, which looks in-depth at the past successes of vaccines, the current role of industry and what needs to happen to move forward. The series was published a few weeks before a separate but related press conference, hosted by the National Foundation for Infectious Diseases (NFID). Although the events were separate, the message was the same: Vaccines save lives, and that message needs to be communicated to the public and policymakers that fund vaccine research.
One of the papers in the series, co-written by Infectious Diseases in Children Editorial Board member Steven B. Black, MD, of Cincinnati Children’s Hospital, focuses on vaccine discovery and translation of new vaccine technology.
In the paper, Black and colleagues said within the past 2 decades, new technologies, including the development of glycoconjugate vaccines against Haemophilus influenzae type b, Streptococcus pneumoniae and, most recently, Neisseria meningitidis, have resulted in virtual eradication of Hib disease, large reductions in morbidity and mortality due to pneumococcal pneumonia and meningitis, and now have the potential to tame meningococcal meningitis and sepsis. The MenAfriVac vaccine, which is the meningococcal A conjugate vaccine developed through the Meningitis Vaccine Project, has led to historic decreases of meningitis A cases in Burkina Faso, Mali and Niger.
The scope of vaccines has increased, with newer vaccines such as the human papillomavirus vaccine providing hope for the prevention of cervical cancer.
Also, newer technologies such as systems biology offer the promise of more efficient identification of safe and effective vaccines, which could lower development costs and thus allow more vaccines to be developed. In an interview with Infectious Diseases in Children, Black said research for yellow fever vaccine has focused on the system’s biology of how immune responses are mounted for this vaccine. This avenue of research could potentially be applied to development of many different types of vaccines. For influenza vaccine development, cell culture-based platforms and oil-in-water adjuvant are being explored.
Molecular genetics and structural biology are also providing avenues to develop vaccines against as yet unpreventable lethal bacterial infections, such as meningococcus B and Staphylococcus aureus. Approaches such as “reverse vaccinology” now allow identification of new target antigens for prevention of disease due to these organisms. In addition, research in human genetics offers the possibility to identify those predisposed to poor immune responses or rare adverse events to vaccines and develop specialized approaches for them.
But, according to Moxon, some challenges to these research avenues remain; notably, pathogens such as HIV and malaria have constantly changing coatings, which make honing in on a target for vaccines a tremendous challenge. He also said production issues continue to pose a challenge because influenza vaccine continues to rely on production in chicken eggs, while newer technologies are being investigated.
Moxon said financing challenges also pose a continued significant threat to these intensified research and development efforts.
It costs about $500 million to bring a new vaccine into the market. In the United States, the cost to fully vaccinate a child has risen from $155 in 1995 to $1,170 in 2007, according to Levine, and reimbursement and insurance schemes have left up to 14% of the country’s children underinsured for all vaccines.
“We are somewhat struggling with getting vaccines to everyone who needs them, but with many more means to overcome those challenges,” Levine said in an interview. “However, in middle- and low-income countries, those obstacles are significant.”
Many African countries are currently struggling to find about 50 cents per dose to purchase a new meningococcal serogroup A conjugate vaccine for prevention of epidemic meningitis, Levine said. In his paper, Levine and colleagues urge middle-income countries to ramp up financial support for vaccines, noting that vaccines are considered by many to be one of the best buys for public health in developing nations because they can protect productive lives and cut the costs of health care and treatment.
“Most of the world’s impoverished individuals are now living in middle-income countries,” Levine said. “Resolution of financing issues for middle-income countries might also affect sustainability of financing for low-income countries through the GAVI Alliance. For example, if lower prices meant that more countries would finance their programs with national funds, then fewer countries would need GAVI Alliance support and donors would be better able to sustain the GAVI Alliance’s funding.”
But the news is not all bleak, he said.
“If you look at data from 1980, you’d see that children in higher-income countries were getting vaccines, but less than one in five children in middle- and low-income countries were getting these vaccines,” Levine said. “However, if you look at the 1990s, those vaccine rates in the middle- and lower-income countries rose, due to an intentional, collective effort by UNICEF and other organizations.”
Advocacy in action
Fortunately, some of that financing is on the way. In June, major public and private donors achieved a milestone in global health by committing funding to immunize more than 250 million of the world’s poorest children against life-threatening diseases by 2015, which will prevent more than 4 million premature deaths.
Donors committed $4.3 billion at the first pledging conference held by the GAVI Alliance. This exceeds an initial target of $3.7 billion, enabling GAVI to reach more children faster than planned and to further accelerate the introduction of new vaccines. A portion of the pledges is conditional upon additional funds being raised in the future. The pledges bring GAVI’s total available resources for the period 2011 to 2015 to $7.6 billion.
The increased support is timely. GAVI recently reported that a record 50 countries applied for vaccine funding during its latest application round — nearly double the previous record in 2007. This new support would allow GAVI to fully fund approved applications, according to GAVI officials.
“For the first time in history, children in developing countries will receive the same vaccines against diarrhea and pneumonia as children in rich countries,” Bill Gates, co-chair of the Bill & Melinda Gates Foundation, said in a press release. “Together, we must do more to ensure that all children — no matter where they live — have equal access to life-saving vaccines.”
And several leading drug makers, including GlaxoSmithKline, Merck, Johnson & Johnson’s Crucell and Sanofi-Aventis, recently offered to cut some of their vaccine prices for developing countries to try to sustain supplies via GAVI.
Black said he was encouraged by this funding, and research from organizations such as GAVI are actually promoting more research by the pharmaceutical companies into other, less-researched vaccine options. Although some pharmaceutical companies have been criticized for opting not to research vaccines, which are traditionally less lucrative than other blockbuster pharmaceuticals, he said research such as GAVI’s is changing that trend.
Levine said the committed funding to GAVI was “great news,” but continued advocacy work is going to be needed to get vaccines to those middle-income countries that may slip through the cracks.
Spreading the word
As funding for vaccine development increases, vigilance will be needed to get the message out about the benefits of vaccines. In large part due to the very effectiveness of the vaccines, the memory of the diseases they are designed to prevent has disappeared from the public, and public confidence in vaccines has consequently deteriorated, according to Heidi J. Larson, MA, PhD, of the London School of Hygiene and Tropical Medicine, and colleagues. In their paper in The Lancet, the researchers analyzed the complex range of factors that are causing loss of public confidence in vaccines.
“Public decision-making related to vaccine acceptance is neither driven by scientific nor economic evidence alone, but is also driven by a mix of psychological, sociocultural, and political factors, all of which need to be understood and taken into account by policy and other decision-makers,” Larson said. “Public trust in vaccines is highly variable, and building trust depends on understanding perceptions of vaccines and vaccine risks, historical experiences, religious or political affiliations, and socioeconomic status.”
Larson and colleagues highlight the powerful effect that the Internet and social media has had on the debate on vaccines, enabling groups either for or against vaccination to organize themselves into highly effective international organizations capable of rapid dissemination of information, including misinformation and rumors. A number of case studies were explored that highlight how vaccine risk concerns were prompted and sustained by individuals.
During 2010, in India, Puliyel and colleagues (representing a cross section of pediatricians, health care activists, public health teachers and bureaucrats) challenged the Indian government’s plan to introduce Hib vaccination into the country’s schedule, on the basis that the disease burden in India did not justify the expense. Larson said Puliyel expressed alarm that some parts of Indian society have taken his views to be part of a broad antivaccination movement, despite that he has been pro-universal vaccination in India all of his working life. In another case, in 2003, religious and political leaders in Nigeria boycotted the polio vaccine, after raising fears it could spread HIV and cause sterility. This boycott was a wake-up call for the Global Polio Eradication Initiative to better engage with these community leaders.
The researchers in that paper concluded: “New methods of communication, dialogue, and engagement are urgently needed across all vaccine stakeholders — vaccine experts, scientists, industry, national and international health organizations, policymakers, politicians, health professionals, the media, and the public. No single player can reverse the vaccine confidence gap.”
In the United States, health officials said that antivaccine groups may be contributing to diseases such as were previously thought eradicated, like pertussis. In 2010, California health officials noted some 9,000 cases of pertussis in that state alone, the highest prevalence of the disease since 1947. And pertussis prevalence rates were high, and continue to be high, nationwide.
“There are a number of reasons why we are seeing more pertussis. First, it is extremely contagious, nearly as contagious as chickenpox. Also, it is difficult to diagnose, in that it might just present as a prolonged cough, and also, our diagnostic tests are not 100% sensitive. Also, vaccination rates are not as strong as they should be,” Mark H. Sawyer, MD, of the University of California at San Diego, said during the NFID press conference, pointing to mistrust of vaccine as a cause. “Up to 90% of unimmunized household contacts will develop pertussis. So everyone needs to work together to prevent transmission of pertussis, particularly to young babies who are at highest risk.”
As with infectious diseases, in which surveillance is essential for disease control, systematic monitoring of dynamic and evolving vaccine rumors, concerns and refusals is crucial to guide prompt responses to build and sustain public confidence. Such a surveillance system is being tested at the London School of Hygiene and Tropical Medicine.
All of the experts interviewed by Infectious Diseases in Children said the momentum to reach more children with vaccines must be maintained, and they have called on GAVI and other global health organizations to expand coverage of immunization programs and accelerate the introduction of new vaccines.
“Vaccines are one of the most remarkable of all health interventions of all time,” Larson told Infectious Diseases in Children. “It is up to us to get that message out and address the issues of public distrust of vaccines.” – by Colleen Zacharyczuk
For more information:
- Levine OS. Lancet. 2011;doi:10.1016/S0140-6736(11)60406-6.
- Moxon RE. Lancet. 2011;doi:10.1016/S0140-6736(11)60766-6.
- Puliyel J. Indian J Med Res. 2009;129: 205.
- TheLancet.com. New decade of vaccines. Available at: www.thelancet.com/series/new-decade-of-vaccines.
Disclosures: Dr. Moxon has received honoraria for work as a board member for Novartis and GlycoVaxyn, and as a consultant for Novartis. Dr. Black is a consultant for Novartis and serves on the Data & Safety Monitoring Board for GSK, Novartis and WHO. Dr. Levine is supported by grants from the GAVI Alliance and the Bill & Melinda Gates Foundation. Drs. Larson and Sawyer report no relevant financial disclosures.
Are we ready for another influenza pandemic?
We better understand the limitations of our current approaches to surveillance, vaccine production, vaccine distribution, and education of the public: 1) the pressing need for faster vaccine discovery and manufacturing capabilities; 2) the need for multiple vaccine manufacturers to prevent reliance on a sole source supplier; and 3) the critical need for coordination between private and public sector entities. So, how have we done? The pandemic resulted in us getting a safe and effective vaccine delivered nationwide in 6 months ... too long, but compatible with the limitations of the current technologies. NIH has released over a billion dollars to facilitate and accelerate new vaccine methods, and cell-based vaccine culture techniques that will allow us to make vaccines in weeks vs. months. Every state, every public health department, and every health care facility now realize the reality that they must have (and now do have) a feasible response plan.
So, we are better off, and yet simultaneously still have a long way to go. For me, one of the most frustrating aspects is that no matter how good or how fast we can deliver a safe and effective vaccine only a minority of the public (and health care workers, unbelievably!) actually accepted getting the H1N1 vaccine. We have much to do to educate all on these vaccines.
Gregory A. Poland, MD, is a professor of medicine at the Mayo Clinic and is director of the Mayo Vaccine Research Group in Rochester, Minn. Disclosure: Dr. Poland reports no relevant financial disclosures.
What was learned from the pandemic of H1N1 influenza? The first lesson learned was that the pandemic could arise anywhere in the world and active global surveillance is needed to detect the next pandemic strain. Second, the population affected varies depending on the previous experience with the circulating strain. In contrast to yearly seasonal influenza, where the morbidity and mortality is greatest in the elderly, in this pandemic attack rates were greatest in younger individuals who had not experienced a similar influenza strain. Third, the pandemic reminded us that pregnant women are always at risk for complications with influenza, but the toll with the pandemic strain was particularly great. Fourth, the impact of prompt antiviral therapy in influenza infected patients was repeatedly shown, highlighting the need for rapid detection and prompt therapy of influenza, particularly for those at the highest risk for complications. Fifth, public acceptance of influenza vaccines, particularly pandemic strains can be extremely challenging. In spite of extensive testing of the pandemic vaccines prior to release, the public was wary about vaccine safety and acceptance was far less than had been expected. Sixth, the vaccines were shown to be efficacious for the prevention of influenza with rates approaching 56% in preliminary US studies. However, the number of cases that would have been prevented with widespread use of the vaccine prior to the pandemic peak would have been greater. The real effectiveness was lower than anticipated because of delays in availability. Seventh, new innovative vaccines can generate higher levels of antibody, and likely greater protection, particularly in young children. The innovative adjuvants added to the H1N1 vaccines in Europe and Canada were excellent examples of how the usual influenza vaccines could be enhanced.
Are we more prepared for the next pandemic? Certainly the lessons learned from the H1N1 pandemic have prepared us for the next one. We are also extremely fortunate that the pandemic was not caused by the avian strain that continues to circulate in a restricted fashion in Asia, since mortality rates with avian influenza approach 50%. The H1N1 pandemic taught us how to prepare pandemic vaccines, but highlighted the need for stock vaccine strains to be immediately available and the need for an even more rapid production. Vaccine delivery systems were enhanced, but also highlighted the need for education and reassurance for the public that the vaccines were safe and effective.
The global seasonal vaccine supply has also increased as a function of the vaccine production activities associated with the pandemic. Let us hope that when another pandemic arrives that we will be even better prepared than we were for the last one.
Kathryn M. Edwards, MD, is an Infectious Diseases in Children Editorial Board member. Disclosure: Dr. Edwards reports no relevant financial disclosures.
We were able to test our well-established US vaccine safety monitoring systems during the recent H1N1 pandemic, and we found the systems to be robust and capable of providing safety information rapidly. This provides enhanced confidence in our systems for monitoring vaccine safety, not only on a routine basis but also when vaccine is distributed rapidly over a short period of time, as occurred during the H1N1 pandemic.
As with any vaccine, the safety findings on adjuvanted influenza vaccines (which were used during the 2009 H1N1 influenza pandemic) are important if such vaccines become more common in future, whether in seasonal influenza vaccines or for the next pandemic.
Claudia J. Vellozzi, MD, MPH, is deputy director of the CDC’s Immunization Safety Office within the National Center for Emerging and Zoonotic Infectious Diseases. Disclosure: Dr. Vellozzi reports no relevant financial disclosures.
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