The results of a clinical trial suggest it is possible to modify the body’s response to an infection with a related virus.
The researchers report in Nature Microbiology that antibodies, under specific conditions, can intensify infection with a virus related to the causal organism. This phenomenon has been postulated as a reason why some patients with second dengue infection develop a more severe disease.
Using two licensed vaccines against related viruses, the investigators demonstrated antibody-dependent enhancement (ADE) clinically and also illustrated that this process may be exploited to boost vaccine effects for stronger immunity.
Vaccines are usually made up of viruses in a non-infectious or weakened state to trigger the immune system’s production of antibodies to fight viral diseases. Largely administered to children, vaccinations are also given to susceptible adults who may have experienced prior infections or vaccinations against related viruses.
This preventive measure is especially critical due to newly emerging viruses belonging to families that commonly affect humans, such as the Zika and dengue viruses. A vaccine against the Zika virus must be able to work in a background of dengue antibodies since dengue, transmitted by the same mosquitoes, is more widespread.
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This study, conducted at the SingHealth Investigational Medicine Unit by researchers at Duke-NUS Medical School and Singapore General Hospital, administered 84 healthy adult volunteers with the Yellow Fever (YF) vaccine only, or the Japanese Encephalitis (JE) vaccine followed by the YF vaccine. Compared with volunteers who received the YF vaccine alone, those given the JE vaccine produced JE antibodies, and exhibited an increased response to subsequent YF vaccination. Specifically, this enhanced response involved prolonged exposure of the YF virus to the body’s immune system, which contributed to the higher levels of YF-neutralizing antibodies and greater protection against YF.
The scientists determined that the enhanced immune response recorded following JE and YF vaccinations was mediated by the increased production of pro-inflammatory agents. They are now working on ascertaining the precise mechanism of the process to generate improved immune responses to vaccinations.
Professor Ooi Eng Eong, senior author of the paper and deputy director of the Duke-NUS Signature Research Program in Emerging Infectious Disease, points out that the lack of knowledge on ADE in humans has hindered dengue vaccine development. The latest findings raise possibilities on how vaccines could be used during pandemic emergencies.
“We might be able to exploit ADE so that what used to be a single dose for a single individual may possibly be used to provide effective immunity for many more and stretch limited supply of some vaccines,” he says.
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“By understanding the exact mechanism by which ADE enhances vaccines, we would also be able to design more effective vaccines that do not require multiple dosages for effective protection. ADE may also be applicable to other virus families beyond the flaviviruses, such as vaccines against influenza and HIV,” adds Jenny Low, senior consultant with the department of infectious disease at Singapore General Hospital and co-corresponding author of the paper.
The growing number of pandemics in recent years calls for the urgent development of effective vaccines. This clinical work elucidates a phenomenon hitherto only tested in the laboratory, serving up new considerations for vaccine design and development. ADE could be a new way to extend the limited supply of some vaccines to protect more of the population.
The team is in talks to evaluate vaccines from pharmaceutical companies to understand how recipients respond to the products and the impact on immunity development.
Source: National University of Singapore
