Improving US programs for the world’s most neglected patients

In this guest post, Dr. John Boslego, director of PATH’s Vaccine Development Global Program, writes about an innovative partnership between the United States and India to develop an oral vaccine against rotavirus diarrhea. I recently had the pleasure of attending an international symposium on rotavirus vaccines where the government of India’s Department of Biotechnology (DBT) and the Indian vaccine manufacturer Bharat Biotech announced positive results from a Phase III clinical trial of an oral rotavirus vaccine that was developed and manufactured in India. Data from the trial showed the vaccine, ROTAVAC®, to be safe and effective in protecting infants against severe rotavirus diarrhea, the most lethal cause of childhood diarrhea. ROTAVAC® represents an important scientific breakthrough against severe rotavirus diarrhea, responsible for approximately 100,000 deaths of small children in India each year. Credit: PATH. However, what’s most extraordinary about this announcement actually may not be the results themselves, but the long and unique road that ROTAVAC® traveled to reach this point. This vaccine is the product of an innovative partnership between the United States and India, involving renowned experts from a range of agencies and sectors across the two countries. The vaccine originated from an attenuated (weakened) strain of rotavirus that was isolated from an Indian child at the All India Institute of Medical Sciences in New Delhi in the mid-1980s. Since then, partners in the vaccine’s development have included DBT, Bharat Biotech, the US National Institutes of Health (NIH), the US Centers for Disease Control and Prevention (CDC), Stanford University School of Medicine, and PATH. Each group has provided its own contribution to the project, ranging from technical assistance on vaccine development and manufacturing the vaccine batches used in clinical trials, to guidance on designing and implementing clinical trials that meet international standards. With the development costs shared by several partners, Bharat Biotech was able to commit to a price of US$1.00 per dose for ROTAVAC®. As such, Bharat Biotech plans to register the vaccine for use in India first. If licensed by the Indian regulatory authority, the vaccine will be a more affordable alternative to the rotavirus vaccines already on the market. This represents an important scientific breakthrough against severe rotavirus diarrhea, responsible for approximately 100,000 deaths of small children in India each year. If licensed, this vaccine could save the lives of thousands of children each year in the country. Bharat Biotech also plans to submit ROTAVAC® for prequalification by the World Health Organization, so it may be procured for subsidized use in the developing world, giving it the potential to have an enormous impact on global public health by reducing rotavirus-related illness and deaths worldwide. I’m proud of the role that PATH has played in reaching this incredible milestone, and I am particularly impressed with how this truly innovative approach to a vaccine development partnership has resulted in the production of a safe and efficacious new rotavirus vaccine, ROTAVAC®.

In this guest post, Dr. Claire Huang, a researcher with the Centers for Disease Control and Prevention’s (CDC) Division of Vector-Borne Diseases, describes a dengue vaccine candidate developed by her team. The vaccine is now being clinically evaluated in field trials. This is the final blog in a four-part series by experts from CDC’s National Center for Emerging and Zoonotic Infectious Diseases. Dengue, a painful and sometimes deadly viral disease transmitted by mosquitoes, threatens more than 2.5 billion people, or 40 percent of the world’s population. Dengue is endemic in at least 100 countries in Southeast Asia, the Pacific Islands, the Caribbean, Central America, South America, and parts of Africa. A recent report in the journal Nature estimated that there are 390 million dengue infections yearly; 96 million of those infections cause moderate to severe illness, and 294 million cause no or mild symptoms. Previous reports also suggested that 500,000 severe dengue hemorrhagic fever cases and 22,000 deaths occur annually, mostly among children. In 2013, the World Health Organization ranked dengue as the fastest spreading vector-borne viral disease. The mosquito vectors of the virus have adapted to living in urban areas, so changes in demographics favor transmission. Puerto Rico, for example, had one of its largest recorded epidemics in 2010, with more than 21,000 reported cases. Several years ago, Florida reported its first cases of locally acquired dengue in 75 years, and the Republic of the Marshall Islands currently is experiencing its first epidemic since 1989. New outbreaks in Angola and Kenya are also being investigated right now by our Division staff. As the world has become more accessible and travel becomes more frequent, the risk from dengue viruses has increased. Large numbers of travelers return from dengue-endemic areas to the United States each year, increasing the possibility of introducing the virus to those parts of this country where the mosquitoes capable of transmitting dengue virus still thrive. Claire Huang (center) and her team (L-R), Janae Stovall, Betty Luy, and Karen Boroughs, in their CDC laboratory in Fort Collins, Colorado. Credit: CDC. I was born and raised in Taiwan, and I saw first-hand how devastating the disease can be. In 1987, South Taiwan had a dengue outbreak. Now, dengue is a common infection, and dengue cases are reported every year. This is how I became interested in dengue research. Vaccination is the best way to protect against mosquito-borne diseases, and it has been my lifelong passion to create a vaccine that will protect people against the crippling illness I witnessed. Despite decades of effort by many scientists to develop a vaccine for dengue, no licensed vaccine is available. Dengue is caused by infection with any of four distinct but related dengue viruses, and a successful dengue vaccine must offer immunity against all four types of the virus. Infection with one type of the virus produces lifelong immunity—but only to that dengue type. Infection with another type of dengue virus increases the chance of developing life-threatening dengue hemorrhagic fever. Typically, an epidemic caused by one dengue virus type is followed a few years later by an epidemic caused by one of the other three types. In most dengue-endemic countries, most teenagers have already been exposed to multiple dengue viruses. My team in the Division of Vector-Borne Diseases in Fort Collins, Colo., has developed a tetravalent dengue vaccine candidate active against all four types of the virus that is now being clinically evaluated in the United States, Colombia, Puerto Rico, Thailand, and Singapore for safety and efficacy. The vaccine is showing promising results in these human clinical trials. The novel technology invented at CDC and used to create the vaccine has been awarded multiple US and international patents. My team has partnered with Inviragen, Inc., a Colorado-based vaccine company, to conduct collaborative research, development, and licensure agreements. Inviragen is manufacturing the vaccine, named DENVax, and is conducting clinical development and testing of the vaccine for human use. The goal is to provide a safe, effective, and affordable dengue vaccine to protect billions of people living in or traveling to dengue-endemic countries. As my team’s efforts to develop this potentially lifesaving vaccine demonstrate, more research in dengue is needed to fully understand the disease and develop effective strategies to prevent and control the disease.