Potent Henipavirus Neutralization by Antibodies Recognizing Diverse Sites on Hendra and Nipah Virus Receptor Binding Protein.

Hendra (HeV) and Nipah (NiV) viruses are emerging zoonotic pathogens in the Henipavirus genus causing outbreaks of disease with very high case fatality rates. Here, we report the first naturally occurring human monoclonal antibodies (mAbs) against HeV receptor binding protein (RBP). All isolated mAbs neutralized HeV, and some also neutralized NiV. Epitope binning experiments identified five major antigenic sites on HeV-RBP. Animal studies demonstrated that the most potent cross-reactive neutralizing mAbs, HENV-26 and HENV-32, protected ferrets in lethal models of infection with NiV Bangladesh 3 days after exposure. We solved the crystal structures of mAb HENV-26 in complex with both HeV-RBP and NiV-RBP and of mAb HENV-32 in complex with HeV-RBP. The studies reveal diverse sites of vulnerability on RBP recognized by potent human mAbs that inhibit virus by multiple mechanisms. These studies identify promising prophylactic antibodies and define protective epitopes that can be used in rational vaccine design.

The recent Nipah virus outbreak in Bangladesh could be a threat for global public health: A brief report.

The Nipah virus is a zoonotic infection that can potentially be transmitted from person to person as well as through ingesting contaminated food. It has a high fatality rate, and no treatment or cure at present. Several nations in South Asia have reported Nipah virus outbreaks occurred during a particular season of the year. Since it was first found in Bangladesh in 2001, there have been a total of 335 people infected with it, and 237 of those people have passed away as a result of their infection. With increased public awareness, community engagement, and preventative measures, this potentially fatal virus has been suppressed. Yet, following a pandemic and a considerable increase in the health burden, the transmission rate continuously increased over a few years, indicating that there is a growing possibility to become a global public health concern. Without effective vaccines and reliable treatment options, its capacity for human-to-human transmission and potential to spread throughout the area could result in a disastrous public health emergency worldwide.

The Immunobiology of Nipah Virus.

Nipah virus (NiV) is a highly lethal zoonotic paramyxovirus that emerged in Malaysia in 1998. It is a human pathogen capable of causing severe respiratory infection and encephalitis. The natural reservoir of NiV, Pteropus fruit bats, remains a continuous virus source for future outbreaks, although infection in the bats is largely asymptomatic. NiV provokes serious disease in various mammalian species. In the recent human NiV outbreaks in Bangladesh and India, both bats-to-human and human-to-human transmissions have been observed. NiV has been demonstrated to interfere with the innate immune response via interferon type I signaling, promoting viral dissemination and preventing antiviral response. Studies of humoral immunity in infected NiV patients and animal models have shown that NiV-specific antibodies were produced upon infection and were protective. Studies on cellular immunity response to NiV infection in human and animal models also found that the adaptive immune response, specifically CD4+ and CD8+ T cells, was stimulated upon NiV infection. The experimental vaccines and therapeutic strategies developed have provided insights into the immunological requirements for the development of successful medical countermeasures against NiV. This review summarizes the current understanding of NiV pathogenesis and innate and adaptive immune responses induced upon infection.

Cooperativity mediated by rationally selected combinations of human monoclonal antibodies targeting the henipavirus receptor binding protein.

Hendra virus and Nipah virus (NiV), members of the Henipavirus (HNV) genus, are zoonotic paramyxoviruses known to cause severe disease across six mammalian orders, including humans. We isolated a panel of human monoclonal antibodies (mAbs) from the B cells of an individual with prior exposure to equine Hendra virus (HeV) vaccine, targeting distinct antigenic sites. The most potent class of cross-reactive antibodies achieves neutralization by blocking viral attachment to the host cell receptors ephrin-B2 and ephrin-B3, with a second class being enhanced by receptor binding. mAbs from both classes display synergistic activity in vitro. In a stringent hamster model of NiV Bangladesh (NiVB) infection, antibodies from both classes reduce morbidity and mortality and achieve synergistic protection in combination. These candidate mAbs might be suitable for use in a cocktail therapeutic approach to achieve synergistic potency and reduce the risk of virus escape.

Nipah: An Interesting stance.

Nipah instead was one of the most fatal outbreaks of diseases in the mankind which was initially assumed as Japanese encephalitis. A multidisciplinary exploration was done at several levels of microbiology, histopathology and genetics which led to the discovery of a new paramyxovirus named Nipah virus (NiV). The disease was primarily identified in Malaysia in 1998 and named after a village, Sungai Nipah. The main mode of transmission in the Malaysian outbreaks was thought to be the consumption of bat's dropping, urine and fruit partially eaten by pigs. In Bangladesh and northeast India, the virus was directly transmitted from bats to human through consumption of raw date palm juice. To limit the epidemic, coordinated efforts by health care providers have become mandatory. This article gives a note about the NiV, its infection and on-going researches on its management strategies. Data were collected using electronic media consisting of articles, books and websites.