Preserved antiviral adaptive immunity following polyclonal antibody immunotherapy for severe murine influenza infection

Abstract

Passive immunotherapy may have particular benefits for the treatment of severe influenza infection in at-risk populations, however little is known of the impact of passive immunotherapy on the formation of memory responses to the virus. Ideally, passive immunotherapy should attenuate the severity of infection while still allowing the formation of adaptive responses to confer protection from future exposure. In this study, we sought to determine if administration of influenza-specific ovine polyclonal antibodies could inhibit adaptive immune responses in a murine model of lethal influenza infection. Ovine polyclonal antibodies generated against recombinant PR8 (H1N1) hemagglutinin exhibited potent prophylactic capacity and reduced lethality in an established influenza infection, particularly when administered intranasally. Surviving mice were also protected against reinfection and generated normal antibody and cytotoxic T lymphocyte responses to the virus. The longevity of ovine polyclonal antibodies was explored with a half-life of over two weeks following a single antibody administration. These findings support the development of an ovine passive polyclonal antibody therapy for treatment of severe influenza infection which does not affect the formation of subsequent acquired immunity to the virus.

An influenza A virus (H7N9) anti-neuraminidase monoclonal antibody protects mice from morbidity without interfering with the development of protective immunity to subsequent homologous challenge

“…Because 3c10-3 does not directly neutralize virus infectivity but acts by limiting virus egress and subsequent cell-to-cell spread, as indicated by our in vitro data (Wilson et al, 2016) and the currently reported reduction of virus lung titers in vivo, an active but attenuated infection is likely established. This allows recognition and subsequent development of effective adaptive immune responses that are capable of protecting against homologous infection and is similar to a study which found that passive immunity with ovine polyclonal antibodies targeting influenza not only protected mice from primary infection but also preserved the development of antiviral adaptive immunity to subsequent viral challenge (Stevens et al, 2016). Interestingly, we observed a reduced anti-NA antibody response as indicated by both ELISA and NAI assays in the 3c10-3 treated mice prior to re-challenge.…”

Fc functional antibodies in humans with severe H7N9 and seasonal influenza

“…Previous work on this cohort showed that the CD8 + T cell response was also impaired in people who died from H7N9 infection (6) and that these subjects commonly had other comorbidities (7). There is a growing interest in passive transfer of anti-influenza Abs in severe influenza, with some efficacy observed in small human studies (43,44) and animal models (45). Both polyclonal immunoglobulin preparations (28) and some monoclonal Abs can have significant Fc-mediated functions across a range of influenza strains (24,25,33).…”

Engineered Recombinant Single Chain Variable Fragment of Monoclonal Antibody Provides Protection to Chickens Infected with H9N2 Avian Influenza

“…We hypothesised that intranasally administered H9 HA-specific scFvs could prevent or limit virus infection, leading to reduced disease symptoms in chickens. Intranasal antibody administration has previously been shown to provide superior protection in mice when compared to systemic delivery, as well as to require lower doses to achieve protective effects [5,48,49]. An alternative delivery method could be via food pallets as some evidence exists on virus replication in gastrointestinal (GI) tract of poultry; however, in most of the cases, LPAI H9N2 poses higher tropism for respiratory tract in chickens and the effect of low pH in GI on antibody stability remains elusive [50][51][52].…”