Advances and perspectives in the development of vaccines against highly pathogenic bunyaviruses

Abstract

Increased human activities around the globe and the rapid development of once rural regions have increased the probability of contact between humans and wild animals. A majority of bunyaviruses are of zoonotic origin, and outbreaks may result in the substantial loss of lives, economy contraction, and social instability. Many bunyaviruses require manipulation in the highest levels of biocontainment, such as Biosafety Level 4 (BSL-4) laboratories, and the scarcity of this resource has limited the development speed of vaccines for these pathogens. Meanwhile, new technologies have been created, and used to innovate vaccines, like the mRNA vaccine platform and bioinformatics-based antigen design. Here, we summarize current vaccine developments for three different bunyaviruses requiring work in the highest levels of biocontainment: Crimean-Congo Hemorrhagic Fever Virus (CCHFV), Rift Valley Fever Virus (RVFV), and Hantaan virus (HTNV), and provide perspectives and potential future directions that can be further explored to advance specific vaccines for humans and livestock.

Looking Beyond the Lens of Crimean-Congo Hemorrhagic Fever in Africa

“…Despite being used domestically, the Bulgarian vaccine has not been approved globally because of safety concerns and the lack of controlled clinical efficacy trials ( 41 ), emphasizing the continuous need for further research on and development of CCHF vaccines. To address the genetic diversity of various CCHFV strains in vaccine development, it is essential to optimize vaccine formulations, evaluate dosing regimens, and identify immunogenic epitopes that confer robust and lasting immunity against CCHFV ( 45 ). Identifying those epitopes is critical for developing vaccines that can defend against CCHFV genetic variants ( 15 ).…”

A mRNA Vaccine for Crimean–Congo Hemorrhagic Fever Virus Expressing Non-Fusion GnGc Using NSm Linker Elicits Unexpected Immune Responses in Mice

“…Crimean–Congo hemorrhagic fever (CCHF) disease is usually caused by bites from ticks carrying Crimean–Congo hemorrhagic fever virus (CCHFV) or direct contact with the blood or tissue of viremia-phase livestock [ 1 ]. Infected patients usually present symptoms of myalgia, fever, nausea, vomiting, and diarrhea in the pre-hemorrhagic period and hematemesis, melena, and somnolence in the hemorrhagic period, with a case fatality rate of around 30% [ 2 , 3 , 4 ]. CCHFV has been reported in Asia, Africa, the Middle East, and Europe [ 5 ] and is divided into the Asia-1, Asia-2, Africa-1, Africa-2, Africa-3, Europe-1, and Europe-2 clades [ 6 ].…”

“…CCHFV belongs to the Nairoviridae family of the Bunyavirales order [ 2 ]. The genome consists of three single-stranded, negative-sense RNA segments: (1) small (S); (2) medium (M); and (3) large (L).…”