Clinical and translational evaluation of vector saliva based vaccination strategies for Zika, Chikungunya, Dengue, Leishmania, Malaria, and other important or emerging vector-borne diseases

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

Mosquito-borne diseases continue to cause significant morbidity and mortality worldwide despite on-going control efforts. In 2015, there were >200 million cases of malaria worldwide, causing nearly half a million deaths, with most of the deaths occurring among children under the age of 5 years. Mosquitoes also transmit arboviruses, including dengue, yellow fever, West Nile virus, chikungunya, Rift Valley fever, Japanese encephalitis, and Zika virus. The recent outbreak of Zika virus in Central and South America, as well as the Caribbean, serves as a reminder of how quickly these viruses can spread and how difficult they can be to control. In 2020 we published a Phase I study of a novel universal mosquito-borne disease vaccine, AGS-V, that modulates the immune system after a mosquito feeding. This vaccine targets the vector saliva and may provide prophylaxis against multiple arboviral and protozoal diseases. The vaccine was found to be safe and immunogenic as described in our publication in Lancet. This publication marks the first time a vaccine targeting mosquito saliva has been tested in humans and the first-time clean mosquito feedings on humans have been performed in the NIH Clinical Center. This study we believe serves as a baseline for this type of vaccine to be developed and opens the door for these types of trials to be done. As a continuation of our close collaboration with LMVR we were awarded an NIH Bench To Bedside award and in 2018 completed enrollment of a follow up clinical study in the NIH Clinical Center to evaluate the effect on the immune response of multiple exposures to the same vector. This study included the evaluation of two species of mosquito as well as sandflies, the vector of leishmania. We expect the final data from this study to be instrumental in further understanding how vaccination strategies that target vector saliva may work in individuals from endemic disease areas. During this past year detailed laboratory analysis was performed, but due to COVID related delays we did not complete the work. We expect to have the results ready to publish early in this next year as work has resumed. During this past year we have completed analysis of a third clinical trial, a follow up study to our initial study of AGS-v an updated version of the vaccine, AGS-v Plus. This Phase Ib study completed enrollment last year in collaboration with LMVR and University of Maryland under a CRADA agreement. We are completing the follow up visits for the study now and plan to have the data ready for publication by early 2022. This study continues the important clinical development of this unique vaccine strategy we initiated studies with in 2018. In addition, we have continued to collaborate with Taia Wang at Stanford University. In this collaboration we continue to investigate aspects of mosquito borne disease immunity and antibody structure and function in order to better understand correlates of protection. By providing clinical samples collected in our trials this collaboration is able to generate interesting data that may help in the further development of novel vaccines and vaccine strategies. As part of this collaboration we applied some of the techniques we have been using to the COVID-19 pandemic as part of this project.