AsianScientist (Dec. 28, 2017) – Scientists in Singapore have discovered that protection against dengue in mouse pups can be enhanced by directly immunizing pups with vaccines that induce an effective killer T-cell response. They published their findings in JCI Insight.
For a long time, a dengue vaccine was the holy grail in dengue research. Now that a dengue vaccine is finally on the market (Sanofi’s Dengvaxia®), other issues have arisen, such as what happens in the babies of vaccinated mothers.
A vaccinated mother passes anti-dengue antibodies to her child during gestation and breastfeeding. These antibodies from the mother should protect the child against infection with the same strain of dengue virus, but have unclear effectiveness against different dengue strains.
In fact, a mother’s antibodies can actually worsen a dengue infection in her baby, causing severe complications such as dengue hemorrhagic fever and dengue shock syndrome. These life-threatening conditions may be accompanied by symptoms such as abdominal pain and leakage of fluids into the lung and internal cavities.
Thus, there is a need to determine whether babies born to dengue vaccinated mothers would be protected or, instead, be at risk of developing severe dengue disease upon infection. In addition, it was unknown whether direct vaccination of these babies would be effective.
In this study, a team of researchers led by Associate Professor Sylvie Alonso from the Department of Microbiology and Immunology at the National University of Singapore’s Yong Loo Lin School of Medicine vaccinated adult female mice with the main constituent (PDK53) of a dengue vaccine that is in clinical development (DENVax).
As they expected, the pups born to these vaccinated mothers had high levels of antibody and were protected against infection by a dengue strain that was very similar to the one used in the vaccine. However, the maternal antibodies did not protect the pups against a different strain of dengue virus. In contrast, they made the disease more severe.
The researchers then went on to vaccinate newborn pups born to immunized adult females with PDK53. They found that the maternal antibodies circulating in the pups prevented the pups’ immune system from producing antibodies specific for dengue virus. This is a known phenomenon, called ‘maternal antibody interference.’
Despite the poor antibody response, the pups were still protected from infection by a different strain of dengue virus. The researchers revealed that this was due to the PDK53 vaccine which had induced protective killer T-cells that recognized and attacked even the different dengue virus strain, thus preventing the pups from developing disease.
These findings suggest that a vaccine that induces an effective killer T-cell response could provide better and broader protection for children of vaccinated mothers than vaccines that rely mainly on antibodies, such as Dengvaxia®. The impact of this work on vaccination strategies will continue to grow as more children are born to mothers who have been vaccinated against dengue infection.
The article can be found at: Lam et al. (2017) Dengue Vaccine-induced CD8+ T Cell Immunity Confers Protection in the Context of Enhancing, Interfering Maternal Antibodies.
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Source: National University of Singapore; Photo: Shutterstock.
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