In the first part of this two-part blog series, I discussed NanoString nCounter® technology. nCounter allows biologists to quantify gene expression using a series of molecular probes. One application of nCounter is in vaccine research. For example, in the first part of this series, I discussed how nCounter is used by researchers to create needle-free vaccines, minimizes doses necessary, and expand our understanding of how the body responds to a vaccine.
In this part, I’ll talk about nCounter in specific disease contexts. First, I’ll talk about how biologists in Australia are using vaccines to protect koalas. Then, I’ll discuss the development of vaccines for Zika and Johne’s Disease.
Protecting Koalas from Disease
Since Europeans arrived down under in 1788, over 80% of the eucalypt forests that koalas rely on for food and home were lost. Habitat loss, in addition to dogs, cars, bushfires, and disease all threaten the koala’s survival.
One such disease threat is from koala retrovirus. Retroviruses are a class of viruses that have an RNA, rather than DNA genome. This can result in endogenization, or incorporation of viral DNA incorporated into the germ cells. Consequently, offspring can inherit the viral DNA from their parents. This means that koalas are at risk for contracting koala retrovirus from either their parents or other koalas.
Infection with koala retrovirus can lead to a higher chance of disease. The development of an effective vaccine is important for protecting koalas. Olusola Olagoke and colleagues are working to develop a koala retrovirus vaccine. In their recent paper, Olagoke and colleagues used nCounter to characterize immune gene expression at pre-vaccination levels, four, and eight weeks after vaccination.
Rather than using a standard panel like the other authors in this blog series, Olagoke and colleagues instead used a custom NanoString probe panel. Among the koalas studied with endogenous koala retrovirus, the authors noted that genes in both the innate and adaptive immune systems were expressed after vaccination. Some genes were downregulated as a result of the vaccine. Olagoke and colleagues’ work provides insight into how koalas with endogenous koala retrovirus respond to vaccination, which will be useful for future work to protect this culturally significant and charismatic animal.
Creating a Zika Virus Vaccine
Zika virus is spread by mosquitoes. Zika virus can pass from an infected mother to her unborn child causing birth defects. There is currently no treatment for Zika infection or vaccine against Zika infection. One challenge researchers face with the development of a vaccine is a lack of understanding of how the vaccine specifically triggered the development of an adaptive immune response.
Clement Yau and colleagues set out to meet this challenge by examining immune system response to mice given a candidate Zika virus vaccine. Yau and colleagues used Mouse Immunology panel and inflammation panel to understand the immune response of mice given the Zika virus vaccine, then exposed to a lethal dose of Zika virus.
Yau and colleagues were interested in achieving sterilizing immunity, or when a virus like Zika is unable to infect the body. Based on their gene expression results, the authors concluded that to achieve sterilizing immunity to Zika virus infection, both the humoral and the adaptive immune systems must be involved. With this new knowledge, future researchers are better equipped to select potential vaccine candidates.
Protecting Cattle Through a Better Johne’s Disease Vaccine
Paratuberculosis or Johne’s disease affects cattle and other ruminants. Johne’s disease is characterized by diarrhea, weight loss, reduced milk production, and early death. Mycobacterium avium subsp. Paratuberculosis is the type of bacteria that causes Johne’s disease. This type of bacteria is related to the types of bacteria that cause both tuberculosis and leprosy in humans.
Approximately 68% of dairy herds within the United States contain at least one cow positive for
Mycobacterium avium subsp. Given the ill health, low milk production, and shortened lifespan of these animals, widespread infection with Mycobacterium avium subsp. Paratuberculosis can cause significant economic damage to farmers.
Although a vaccine for Mycobacterium avium subsp. Paratuberculosis currently exists for cattle, it does not provide complete protection for animals. Therefore, there is a need to develop a better vaccine.
Sandeep Gupta and colleagues set out to do exactly that, using NanoString nCounter along the way. Unlike the RNA-based vaccine discussed in Part 1 of this blog series, Gupta and colleagues used protein particles in their vaccine. Then they assessed how well these protein particles induced an immune response.
Using the nCounter Mouse Immunology Panel, PlexSet-24, and the nCounter Analysis System, Gupta and colleagues compared the immune response of mice vaccinated with control, standard, and experimental vaccines. Gupta and colleagues concluded that the experimental vaccines worked as well as the standard vaccine at triggering an immune response. Overall, the author’s findings suggest that protein particles can be an effective method of vaccination against Mycobacterium avium subsp. Paratuberculosis.
In this blog series, I explored how biologists are using NanoString nCounter to improve vaccines. Quantifying gene expression with nCounter technology provides invaluable insights to scientists studying vaccines. This includes everything from the basic science insights provided by Catherine Collignon and colleagues to making vaccines more appealing to those with fear of needles, such as the work to produce a needle-free HIV vaccine by Bridget Fisher and colleagues or a highly effective one-dose COVID-19 vaccine by Ruklanthi de Alwis and colleagues.
In this second part, I discussed applications of nCounter to vaccine development to treat specific diseases, including Koala retrovirus, Zika, and Johne’s Disease. Olagoke and colleagues are using vaccines to protect their native Koala populations from retrovirus infection. Work by Clement Yau and colleagues lays the groundwork for the development of the first Zika virus vaccine. To protect the health and welfare of ruminants, Sandeep Gupta and colleagues are working to develop a better vaccine for Johne’s Disease.
For Research Use Only. Not for use in diagnostic procedures.