As part of our nation’s overall pandemic preparedness strategy, HHS set a preparedness goal of establishing and maintaining a stockpile of bulk vaccine antigen and adjuvants for influenza viruses with pandemic potential to vaccinate 26 million people immediately after a pandemic is declared. BARDA began pre-pandemic influenza vaccine procurement in 2005 for vaccines that would provide protection against emerging avian influenza H5N1 viruses posing a significant pandemic threat. But a decade later we were compelled to ask how long would those stored vaccine components continue to be safe and effective at providing protection and when would they need to be replaced? The results of the “BARDA Ready In Times of Emergency” (BRITE) study have just been finalized. The study is the first of its kind in the world and provided the data needed to answer that important preparedness question.
H5N1 influenza vaccine stored for more than a decade in the National Pre-Pandemic Influenza Vaccine Stockpile (NPIVS) is still safe and immunogenic.
BARDA and ASPR are committed to protecting people from 21st century health security threats while being a good steward of taxpayer dollars. By knowing how long carefully stored influenza vaccine antigen and adjuvants remain safe and immunogenic, we can reduce long term preparedness costs while ensuring that we have stockpiled the pandemic influenza vaccine antigens and adjuvants needed to respond to an influenza pandemic.
Influenza vaccines work by stimulating the body’s immune system to produce antibodies that block the virus from attaching to cells in the human respiratory system, including lungs and bronchial tubes. Antigen is the part of vaccine that stimulates the immune system, and adjuvant allows less antigen needed to stimulate the immune system. The BRITE Study is the first to show that influenza antigen and adjuvant maintain their functional integrity and generate immune system responses even after being stored for an extended period.
BARDA established the NPIVS program in 2005 as a pillar of national pandemic influenza preparedness and response, aiming to maintain homeland and national security, protect workers essential to maintain essential community and healthcare services, as well as young children, pregnant women and other vulnerable populations. At that time, H5N1 was still a new version of the influenza virus and almost 60 percent of people who were confirmed to be infected between 2008 and 2013 died from the disease, according to the World Health Organization. The good news is that the virus hasn’t spread efficiently between people, and the number of cases where the virus jumps from birds to people in close contact with infected birds has been falling. The bad news is that sporadic cases of the virus in people have continued in Asia and the threat persists as long as the virus continues to circulate in birds. Our overriding concern is that the virus could mutate in a way that makes spreading from person to person easy.
Before the completion of this study, we had no clinical evidence that pre-pandemic influenza vaccines stored for long periods of time would be safe or would elicit the expected immune responses in people. This study’s results mean that our earliest pre-pandemic vaccines remain at-the-ready to respond to an H5N1 influenza pandemic and that means the U.S. is better prepared for public health emergencies.
In 2015, we tasked a member of BARDA’s clinical studies network, PPD Development, LP, of Wilmington, North Carolina, to conduct Phase 1 and 2 clinical trials to assess the ongoing safety and immunogenicity of antigen stored in bulk in the stockpile since 2005 for the H5N1 strain called influenza A/Vietnam/1203/2004, as well as MF59 adjuvant which had been stored in the stockpile for more than five years either in bulk or in glass vials ready to use. Vaccine antigens and adjuvants stored in bulk in the stockpile were formulated at the appropriate concentrations and dispensed into sterile multiple or single dose glass vials for use in the clinic.
The study tested how well two doses of the inactivated monovalent vaccine, designed to protect against a targeted virus strain, stimulated immune systems in people ages 18 through 64. Those on the front lines of containing a pandemic, such as healthcare workers, law enforcement officers, and first responders, are at increased of exposure and are likely to be in that age group.
The stockpiled pre-pandemic influenza vaccines were well-tolerated with or without the MF59 adjuvant. The study’s volunteer participants experienced just the typical soreness or red spot at the injection site like people often have with vaccines, but no serious side effects.
Even the oldest stockpiled H5N1 vaccine saw no drop in immunogenicity. As we expected, the adjuvanted vaccine stimulated a greater immune response than the unadjuvanted vaccine. Our study also found that the stockpiled H5N1 vaccine elicited a cross-reactive antibody response, which means the vaccine also worked well in preventing infection from other strains of the H5N1 virus.
The knowledge gained from the BRITE study is being leveraged in an ongoing clinical study conducted by BARDA’s clinical studies network to assess heterologous prime/boost strategies for pandemic vaccine deployment. In this study, subjects receive a ‘prime’ (first vaccination) with a vaccine against one strain, and a ‘boost’ (second dose) with a vaccine against a second, different, strain.
Earlier studies suggested that heterologous prime and boost vaccination regimens, particularly those administered with adjuvant, may be superior to homologous prime and boost vaccination regimens in generating cross-reactive immune responses to divergent influenza viruses. This ‘heterologous’ prime/boost strategy could increase the versatility of the NPIVS, decreasing maintenance costs substantially.
The approach also increases flexibility operationally--in a pandemic, people could be primed once (or twice) with a stockpiled vaccine, while a ‘matched’ vaccine is being manufactured to be used as the ‘boost’-allowing more individuals to be vaccinated faster. These studies are critical to inform decisions on the strategic value of the NPIVS and provide direct evidence to inform pandemic preparedness strategies.
These clinical studies are revealing the value-added by innovative approaches to leverage this national treasure - the NPIVS. You can read the BRITE study, which was published in the peer-reviewed journal Vaccine, to learn more. We know how important it is for emergency planners, responders, and healthcare providers to understand the safety and effectiveness of the drugs, vaccines, and diagnostics made available by BARDA in partnership with private industry. To learn more about pandemic influenza planning and tools, check out the National Pandemic Strategy and 2017 Update of the Pandemic Influenza Plan.