Antibody Prophylaxis and Therapy against Nipah Virus Infection in Hamsters

Abstract

Nipah virus (NiV), a member of the Paramyxoviridae family, causes a zoonotic infection in which the reservoir, the fruit bat, may pass the infection to pigs and eventually to humans. In humans, the infection leads to encephalitis with >40 to 70% mortality. We have previously shown that polyclonal antibody directed to either one of two glycoproteins, G (attachment protein) or F (fusion protein), can protect hamsters from a lethal infection. In the present study, we have developed monoclonal antibodies (MAbs) to both glycoproteins and assessed their ability to protect animals against lethal NiV infection. We show that as little as 1.2 g of an anti-G MAb protected animals, whereas more than 1.8 g of anti-F MAb was required to completely protect the hamsters. High levels of either anti-G or anti-F MAbs gave a sterilizing immunity, whereas lower levels could protect against a fatal infection but resulted in an increase in anti-NiV antibodies starting 18 days after the viral challenge. Using reverse transcriptase PCR, the presence of NiV in the different organs could not be observed in MAb-protected animals. When the MAbs were given after infection, partial protection (50%) was observed with the anti-G MAbs when the animals were inoculated up to 24 h after infection, but administration of the anti-F MAbs protected some animals (25 to 50%) inoculated later during the infection. Our studies suggest that immunotherapy could be used for people who are exposed to NiV infections.

Recombinant Nipah Virus Vaccines Protect Pigs against Challenge

“…High levels of antibodies were induced by all vaccines, with ALVAC-G and ALVAC-F/G inducing higher neutralizing titers than the ALVAC-F vaccine. Previous work by Guillaume et al (17,19) indicated that antibodies against the G and F proteins have a crucial role in protection against NiV. The previously published vaccine study with golden hamsters using vaccinia virus vector reported an increase in antibody titers postchallenge, as detected by virus neutralization at 11 dpi (by ELISA at 5 dpi), and a decline at 18 dpi (17).…”

“…It cannot be excluded that in case of the ALVAC-F/G group, where even the viral RNA was not detected, the vaccination led to sterile immunity. The presence of preexisting high levels of neutralizing antibodies at the time of challenge can, in case of NiV, lead to sterile immunity, as demonstrated by Guillaume and others (19).…”

Feline Model of Acute Nipah Virus Infection and Protection with a Soluble Glycoprotein-Based Subunit Vaccine

“…It is almost without exception that all neutralizing antibodies to enveloped viruses are directed against the virus' envelope glycoproteins. Anti-G MAbs have been shown to be exceptionally potent in neutralizing NiV-and HeV-mediated fusion, as well as live virus infection (40), and a greater potency of NiV anti-G over anti-F MAbs in conferring passive protection of hamsters from NiV disease has recently been demonstrated (23).…”

The Central Role of the Matrix Protein in Nipah Virus Assembly and Morphogenesis

“…Peptides designed to bind the F protein and block formation of the 6-HB inhibit HeV and NiV envelope glycoprotein-mediated membrane fusion in vitro (11)(12)(13). This mechanism of fusion Humoral immunity can clearly offer significant antiviral benefits, since hamsters were protected by passive transfer of antibodies against either NiV F or G (47,48). These studies suggest that immunization directed against the henipavirus envelope glycoproteins may be an effective vaccine strategy in humans or livestock.…”