Vaccination with Rift Valley fever virus live attenuated vaccine strain Smithburn caused meningoencephalitis in alpacas

Abstract

Rift Valley fever (RVF) is a zoonotic, viral, mosquito-borne disease that causes considerable morbidity and mortality in humans and livestock in Africa and the Arabian Peninsula. In June 2018, 4 alpaca inoculated subcutaneously with live attenuated RVF virus (RVFV) Smithburn strain exhibited pyrexia, aberrant vocalization, anorexia, neurologic signs, and respiratory distress. One animal died the evening of inoculation, and 2 at ~20 d post-inoculation. Concern regarding potential vaccine strain reversion to wild-type RVFV or vaccine-induced disease prompted autopsy of the latter two. Macroscopically, both alpacas had severe pulmonary edema and congestion, myocardial hemorrhages, and cyanotic mucous membranes. Histologically, they had cerebral nonsuppurative encephalomyelitis with perivascular cuffing, multifocal neuronal necrosis, gliosis, and meningitis. Lesions were more severe in the 4-mo-old cria. RVFV antigen and RNA were present in neuronal cytoplasm, by immunohistochemistry and in situ hybridization (ISH) respectively, and cerebrum was also RVFV positive by RT-rtPCR. The virus clustered in lineage K (100% sequence identity), with close association to Smithburn sequences published previously (identity: 99.1–100%). There was neither evidence of an aberrant immune-mediated reaction nor reassortment with wild-type virus. The evidence points to a pure infection with Smithburn vaccine strain as the cause of the animals’ disease.

Rift Valley Fever Virus—Infection, Pathogenesis and Host Immune Responses

“…A few of the vaccinated individuals died and histopathological examination revealed meningoencephalitis and RVFV antigens in the brain. A sequence analysis confirmed the identity of the Smithburn strain isolated from the cerebrum of the diseased alpacas and excluded natural RVFV infection as the cause of death [ 115 ].…”

Advancements in Rift Valley fever vaccines: a historical overview and prospects for next generation candidates

“…The Smithburn vaccine, for example, retains residual virulence, which can lead to spontaneous abortions, stillbirths, or fetal death in pregnant ewes, cows, or does, as well as lethal viral meningoencephalitis in young and adult alpacas 73 , 74 , 93 , 94 . Similarly, the Clone 13 vaccine has a potential risk of infecting the placenta and fetuses, leading to stillbirth, fetal malformation, or viral RNA detection in fetuses 78 .…”

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

“…The modified Smithburn vaccine was generated via serial passage of RVFV in a mouse brains and embryonated chicken eggs, and then passaged in BHK-21 cells to finally formulate the attenuated vaccine. The Smithburn animal vaccine has been sold in Eastern Africa and Saudi Arabia ( Faburay et al., 2017 ), but alpacas have been found dead after vaccine administration ( Anthony et al., 2021 ). Clone-13 virus was isolated from human with a 69% truncation in the non-structural protein NSs ( Muller et al., 1995 ), the vaccine was proven safe in livestock such as sheep, goats and cattle ( Sindato et al., 2021 ), but the occurrence of fetus malformations and stillbirths mean that the vaccine can induce serious side effects ( Makoschey et al., 2016 ).…”