On episode 258 of the podcast “This Week in Microbiology”, Vincent Racaniello, Elio Schaechter, Michele Swanson, and Michael Schmidt discussed two main topics focused on anti-genetic variation within dengue virus serotypes and how a novel mRNA vaccine could induce antibodies against tick proteins to prevent transmission of Lyme disease. The first portion of the episode discussed dengue, which is a single-stranded, enveloped RNA virus that causes over 50 million known cases per year. There are four different serotypes, or distinct variations, of dengue that lead to infection in humans. With the rate of infection and different serotypes, understanding more about the immunology of dengue and especially the variation between these serotypes is very important.
One of the main topics discussed was whether antigenic variation made the dengue virus more fit. To assess if there was a fitness advantage with the dengue serotypes, studies looked at the pattern of serotypes from over 8,000 infections during outbreaks in Southeast Asia from 1970 to 2015. It was concluded that antigenic fitness is a major driver of dengue infection population genetics from year to year. Recovery from dengue infection is believed to provide lifelong immunity against that specific serotype. However, cross-immunity, the protection against a given pathogen resulting from immunity acquired from past exposure to a related pathogen or its antigens, of one dengue serotype to the other serotypes after recovery is only partial and temporary. Subsequent infections by other serotypes increase the risk of developing more severe dengue. Research showed that protection against a dengue serotype dropped 63% each year for the first two years following a dengue infection. I think understanding more about the serotypes and population genetics as performed in this study could be greatly beneficial in further development of treatments or a vaccine against dengue. Similar to the mutating variants of SARS-CoV-2 and the various influenza strains we encounter each year, understanding and being able to predict prominent serotypes of dengue could help reduce the rate of infections.
The second story in this episode of “This Week in Microbiology” focused on the creation of an mRNA vaccine that induces antibodies against tick proteins and prevents the transmission of Lyme disease, as described in a recent publication (Sajid, A. et al). Black-legged ticks transmit the bacteria Borrelia burgdorferi, which causes Lyme disease. The authors of the paper aimed to develop a new tool to prevent the spread of Lyme disease: a vaccine that stops ticks from feeding properly once they latch onto a host’s skin, which stops them from transmitting B. burgdorferi. Guinea pigs can develop a natural resistance to tick bites after being repeatedly bitten. At the tick bite sites, guinea pigs develop an inflamed, red welt and the immune reaction interferes with the tick’s ability to continue drinking the blood of its host. Evidence suggests that humans can also build up similar resistance to ticks. Building off of this idea of tick immunity, researchers sought to develop a vaccine to help humans become better protected from tick-borne pathogens like B. burgdorferi.
When a tick feeds, it takes time for the bacteria to be transmitted so the tick must remain attached for 36-48 hours. The tick’s spit helps it avoid discovery during feeding because the saliva contains proteins that suppress the host’s immune response, which reduces the amount of pain and inflammation triggered by the bite. The authors developed an mRNA vaccine using a complex blend of 19 different tick salivary proteins to help provide host protection specifically against those proteins. The goal of the vaccine was to give the host the chance to see these antigens first, before being bitten, in order to develop immunity. To test the vaccine, guinea pigs were immunized and their blood was tested for antibodies against the salivary proteins. The authors found antibodies against 10 out of 19 of the proteins two weeks after vaccination, showing an antibody-specific immune response. To further test the vaccine, the researchers placed black-legged ticks on the guinea pigs to assess if the bites would trigger an immune response. The vaccinated guinea pigs developed substantial redness around the tick bites in comparison to the unvaccinated guinea pigs which showed minimal redness. After 48 hours, some of the ticks began to detach from the vaccinated guinea pigs and 80% had completely detached after 96 hours. In a final experiment to test the vaccines’ ability to reduce the risk of Lyme disease, B. burgdorferi-positive ticks were placed on guinea pigs. In the unvaccinated guinea pig group, 6 out of 13 tested positive for B. burgdorferi but all of the vaccinated guinea pigs tested negative. This showed that not only could the vaccine mount an immune response against tick bites, it could also prevent the spread of Lyme disease in guinea pigs.
In my opinion, the study of dengue serotypes and tick mRNA vaccines present two crucially important areas in global host-pathogen interactions and infections. Understanding the patterns and differences between the dengue serotypes provides new insight into predicted outbreaks and potential treatments for those infected. The novel tick mRNA vaccine shows great potential at providing immunity to a variety of tick-borne pathogens that cause disease in humans. Future directions can focus on targeting the other 9 salivary proteins where immunity wasn’t detected in guinea pigs and then preparing the mRNA vaccine for humans.
References:
- Sajid, A. et al. mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent. Sci.Transl Med. https://doi.org/10.1126/scitranslmed.abj9827 (2021)
