Three vaccines that could have a major impact on global public health the Ebola vaccine, Malaria vaccine and Dengue Fever vaccine are working toward regulatory approval. As we are thankful that many other terrible diseases have either been either eliminated or brought under control by vaccines – small pox, rabies, measles, mumps, rubella, just to name a few; we also look forward to new vaccine targets that can also benefit public health in major ways.
Ebola has been much in the news as we are in the middle of the largest Ebola outbreak in history. Despite awareness of the virus since the first outbreak in Zaire in 1976, there hasn’t been a huge push to develop a vaccine. While some companies have worked on developing a vaccine or therapeutic for the disease, development requires a great deal of investment and the outbreaks have been usually relatively small. Thus making companies reluctant to invest significant resources. Due to the large scale of the current outbreak and the threat it poses there has been renewed interest in developing a vaccine as soon as possible.
Ebola is a deadly diseased caused by one of the Ebola virus strains of which there are five identified strains (four impacting humans). The disease causes flu-like symptoms initially then the person develops more serious symptoms that can include vomiting, diarrhea, low blood pressure and bleeding. As a result, multi-organ failure and death can occur.
There are six Ebola vaccine candidates working toward approval. I have summarized each below.
Closest Candidates to Approval:
GSK has launched a Phase I study in the US, UK and Mali; results of the study are expected by the end of 2014. If the Phase I study is successful the next stage of development would be to begin vaccination of frontline healthcare workers in the three primary affected countries – Sierra Leone, Liberia, and Guinea. The hope would be to begin these vaccinations in early 2015 and GSK has begun manufacturing 10,000 additional doses for this vaccination effort.
GSK acquired the vaccine through acquisition of Okairos in 2013. According to a recent article in Science, Okairos is producing the vaccine in a human cell line in up to 200-liter GE Healthcare WAVE bags and it is estimated that it will take about two months to manufacture the 10,000 doses. In the same article Okairos founder Riccardo Cortese says “with an investment of about $10 million, they could convert their facility to process several 400-liter bags simultaneously in as little as 3 months. At that scale, he predicts they could make 100,000 doses per month.”
In September, NewLink Genetics announced that they had received FDA approval to begin Phase I trials of their Ebola vaccine after promising results in non-human primates. According to NewLink’s press release the “vaccine platform is based on attenuated strains of vesicular stomatitis virus, a common animal virus, modified to express an Ebola virus protein that is non-pathologic in primates and mice.”
Earlier this month, Johnson & Johnson (Janssen Pharmaceuticals) announced up to 200 million to further their Ebola vaccine candidate. The vaccine was developed through a research collaboration with the National Institutes of Health (NIH) and is a combination of a vaccine from Janssen and a vaccine from Bavarian Nordic. Studies in healthy volunteers from Europe, the US and Africa are planned to begin in January. Their goal is to manufacture over a million vaccines in the next few months using the PER.C6 cell line.
Inovio announced in September that they had collaboration with GeneOne Life Science to begin a Phase I clinical study of their vaccine candidate in the first half of 2015.
Protein Sciences, the manufacturers of FLUBLOK, are working on an ebola vaccine candidate. As of early October, they were hoping to begin animal testing in December.
Vaxart has developed an oral vaccine in tablet form, which would have benefits in terms of shipping, storage and delivery over injected vaccines. This vaccine is currently being tested in non-human primates. They will seek to begin human trials in 2015.
Malaria is a mosquito born parasitic disease that if left untreated causes death. The CDC states that in 2010, “an estimated 219 million cases of malaria occurred worldwide and 660,000 peopled died, most (91%) in the African region. Hardest hit are African children where it is estimated that a child dies every minute from malaria. Current treatment options for malaria include anti-malarial medication and preventative measures, such as insecticidal nets and insect spraying. However, the malarial parasites are showing resistance to the medications. There are four parasite species responsible for malaria in humans, with two of these – plasmodium falciparum and plasmodium vivax most common.
In July, GSK applied for regulatory approval of the world’s first malaria vaccine. In the article GSK Seeks Approval for World’s First Malaria Vaccine, published in Reuters it was stated that GSK has been working on the vaccine for 30 years and will be focused for use in African children. GSK has been working with the non-profit organization PATH Malaria Vaccine Initiative on the vaccine and it has also been supported by grants from the Bill & Melinda Gates Foundation. The vaccine, RTS,S is a recombinant subunit vaccine produced in and purified from yeast and contains an adjuvant.
The vaccine is effective against plasmodium falciparum the most deadly and one of the most common parasite species, particularly in Aftrica where the vaccine is being targeted. The vaccine contains an adjuvant as well. There has been some criticism about the effectiveness of the vaccine. According to a PATH Malaria Vaccine Initiative FAQ “The latest results show that among children aged 5-17 months and infants 6-12 weeks of age at first vaccination, vaccine efficacy against clinical malaria after 18 months of follow up was 46% and 27% respectively.” However given that the number of children effected is so high, the vaccine still has the potential to save many lives despite the lower efficacy rates and can improve outcomes when coupled with other preventative measures such as spraying for mosquitos and bed nets.
Dengue Fever Vaccine
Dengue is the world’s fastest growing tropical disease with the World Health Organization reporting 50-100 million cases worldwide. Of these cases, WHO estimates 500,000 develop into Dengue Hemorrhagic Fever, a more severe form of the disease, and 22,000 deaths which occur mostly in children. The Dengue virus is transmitted by mosquitos and currently has no treatment except supportive care and preventative measures to reduce the chance of mosquito bites.
At the end of July, Sanofi Pasteur announced that they were planning to file for approval of the first dengue vaccine in first quarter 2015. In the Reuter’s article Sanofi Sees First Dengue Vaccine Filings in the First Quarter of 2015, it was stated that the vaccine cost 1.74 billion to develop and they are estimating manufacturing 100 million doses a year. Target countries include Mexico, Brazil, Columbia, Singapore and Malaysia. The article states that the vaccine provides “moderate protection” from the virus, but there are still questions about its efficacy.
The vaccine is a combination of 4 chimeric vaccines manufactured in vero cells.
Right behind Sanofi is Takeda, who recently purchased the vaccine company Inviragen, which included in their product portfolio a Dengue vaccine called DENVax. Also a four-strain vaccine, it is currently in clinical trials, but some have estimated possible approval of the vaccine in late 2016-2017 timeframe.
Tribute to a Vaccine Innovator
Yesterday Jonas Salk would have celebrated his 100th birthday. Salk was truly an innovator, who while Director of the Virus Research Library at the University of Pittsburgh, discovered that the poliovirus could be killed with formaldehyde and still trigger an immune response. Subsequently, Salk developed the polio vaccine in the 1950’s and as a result of widespread vaccination efforts, polio was declared eliminated from the United States in 1979 and the Americas in 1994. Polio is a devastating disease and according to the CDC, “in the late 1940s to the early 1950s, polio crippled an average of more than 35,000 people in the United States each year; it was one of the most feared diseases of the twentieth century.” The polio vaccine was a discovery that he never patented. He later went on to found the Salk Institute in 1967.
Viral outbreaks like the current Ebola outbreaks are reminders of the importance of vaccines and the great gifts that Dr. Salk and other pioneers have given us with the reduction and eradication of some of the worst diseases in history. It is hard to imagine the kind of world it would be without these vaccine pioneers. – “Innovators who Paved the Way for Modern Vaccines.”