"Today, the same researchers — who hail from the World Health Organization, Guinea’s Ministry of Health, Public Health England, and other international partners — have unveiled their final results in the Lancet, and they’re just as remarkable. The vaccine was tested in a trial involving nearly 12,000 people in Guinea and Sierra Leone during 2015 and 2016. Among the 5,837 people who got the vaccine, no Ebola cases were recorded. By comparison, there were 23 Ebola cases in the control group that had not gotten the vaccine."The trial was conducted in two parts. In the first part, because the number of people being exposed to the virus had dramatically declined due to the success of public health measures combating the disease, the researchers focused on people who were in close proximity to any infected individuals. These high risk subjects were vaccinated either immediately or after a three-week delay. The three-week delay group served as the negative control. In addition, there were also many people who signed up for the program but never showed up to receive the vaccine, and they too represented part of the control group.
Then because the interim results of this initial "ring vaccination" protocol (i.e. only those people in a contact "ring" of an infected person were part of the study) were so good, they extended the vaccination to the broader population. Altogether there were 3775 + 7995 = 11770 total participants. 3775 were vaccinated immediately, whereas 7995 either received a delayed vaccination or were not vaccinated at all. Among the 3775 who were immediately vaccinated, there were 0 cases of Ebola Virus Disease (EVD); among the 7995 control subjects, there were 34 cases. Based on these data, the authors estimated the range of effectiveness to be between 77% to 100%. At least so far with no immediately vaccinated person becoming infected and falling ill, the vaccine appears to be 100% effective (i.e. toward the high end of this range). These human clinical results matched the preclinical data in non-human primates which showed complete protection from EVD by the vaccine.
The vaccine is named rVSV-ZEBOV because it is based on the vesicular stomatitis virus (VSV) which belongs to the same viral family as rabies virus (QH). In humans, VSV is relatively harmless causing flu-like symptoms, and the vaccine is an attenuated (weakened) version of the virus. The r in rVSV signifies that scientists have genetically engineered VSV to express a key Ebola glycoprotein (envelope protein) on its surface. As a result, when injected into a subject, the vaccine will elicit an immune response (i.e. antibodies) not only against VSV, but also against the expressed Ebola protein providing protection against future exposure to Ebola virus. The ZEBBOV part of the vaccine name is an abbreviation for Zaire EBOla Virus; the virus is thought to have originated in the country of Zaire (now called the Democratic Republic of Congo).
As with any medical treatment, it is important to assess any adverse side-effects. About half of the vaccinated individuals reported at least one adverse event (AE), but the vast majority were mild (e.g. headaches, fatigue, muscle pain) perhaps related to the "flu-like symptoms" of a VSV infection. There were 80 serious adverse events (SAEs) which may require hospitalization, but only two were deemed related to the vaccine, and in both cases the patients recovered completely. This safety profile is very encouraging given the life-threatening nature of EVD. However, as with any vaccine, one wants to minimize the number of even mild adverse events.
The biggest remaining question is the long-term effectiveness of the vaccine (Vox):
'And questions about the vaccine’s long-term effectiveness remain. "One question that has not been adequately addressed, even in nonclinical studies with any Ebola virus vaccine, is with regard to durability — is the vaccine long-lasting?" wrote Thomas Geisbert, an Ebola virus and vaccine expert from the University of Texas Medical Branch in Galveston, in an accompanying editorial. "Is it still protective, for example, 2–3 years after the vaccination?"If the duration of the vaccine is relatively short (say, 2-3 years), then one option is to provide a booster shot.
For those who do become infected by Ebola Virus (EV) despite the existence of a vaccine, the search continues for better treatments. As I described in a previous post, the the most promising drug is ZMapp, which is a cocktail of three monoclonal antibodies that are targeted against Ebola virus proteins. Whereas the vaccine induces your body to make antibodies against EV proteins, the ZMapp drug acts as a synthetic antiserum directly providing anti-EV antibodies.
In the latest trial, ZMapp showed modest (albeit not statistically significant) efficacy. Among people stricken with EVD, there was 78% survival with ZMapp plus standard of care (22% mortality) and 63% survival with standard of care alone (37% mortality). Note that improvements in standard of care have reduced the mortality rate from the previous 50-90%. Close to 80% survival is impressive; further improvements in treatment or perhaps combining ZMapp with other drugs could potentially increase survival to 90% or higher.
Regardless, if the outstanding performance of the rVSV-ZEBOV vaccine holds up, then public health officials will have an incredibly powerful weapon against EVD. As soon as anyone comes down with disease symptoms, then all those within a certain contact radius can be given the vaccine including medical staff. preventing further spread. Already, researchers observed that the limited trial reduced the number of subsequent infections even though only a small number of people were vaccinated. More wide-spread vaccination would completely contain any small outbreaks. Let's not get too far ahead of ourselves, but it appears as though Ebola Virus will no longer pose a major threat to the World.
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