The mucosal humoral immune response of the horse to infective challenge and vaccination with Equine herpesvirus‐1 antigens

Abstract

Summary Equine herpesvirus‐1 (EHV‐1) remains a frequent cause of upper respiratory tract infection and abortion in horses worldwide. However, little is known about the local antibody response elicited in the upper airways of horses following exposure to EHV‐1. This study analysed the mucosal humoral immune response of weanling foals following experimental infection with virulent EHV‐1, or vaccination with either of 2 commercial vaccines. Twenty weanlings were assigned to 5 groups and were inoculated with, or vaccinated against, EHV‐1 following different regimens. Finally, all weanlings were simultaneously challenged intranasally with virulent EHV‐1 Army 183 (A183). Nasal wash and serum samples were collected at regular intervals until 13 weeks after final challenge. Nasal washes were assayed for EHV‐1‐specific equine IgGa, IgGb, IgG(T), IgA, IgM and total virus‐specific antibody using an indirect, quantitative ELISA. Total serum antibody responses were also monitored, and clinical signs of EHV‐disease were recorded for each individual. Virus‐specific IgA dominated the mucosal antibody response elicited in weanlings inoculated with A183, being detectable at up to 3.1 μg/mg total IgA 13 weeks after challenge. Neither inactivated EHV‐1 administered i.m., nor attenuated EHV‐1 administered intranasally induced detectable mucosal antibodies. EHV‐1‐specific mucosal antibodies impeded EHV‐1 plaque formation in vitro. Such virus‐neutralising antibody probably contributes to a reduction of shedding of EHV‐1 from the respiratory tract of virus‐infected horses.

Equine Herpesvirus Type 4 UL56 and UL49.5 Proteins Downregulate Cell Surface Major Histocompatibility Complex Class I Expression Independently of Each Other

“…The immune response to EHV-4 infections remains poorly understood, which is partly caused by the lack of immunologically and/or virologically naïve natural hosts (35,64). As with other respiratory infections, mucosal antibodies and/or cell-mediated immunity may play a role in controlling EHV-4 infections (14). However, it is known that protective immune responses established after either infection or vaccination are shortlived and incomplete (60,74).…”

Immunological Correlates of Vaccination and Infection for Equine Herpesvirus 1

“…EHV-specific IgG isotyping, first performed on nasal washes in a study reported by Breathnach et al (5), has been adapted to assess the isotypes and relative abundances of EHV-1-specific antibodies in horse sera in a nonhazardous and efficient manner (13). We previously showed that an inactivated vaccine promoted an IgG3/5 response, whereas protective immunity from a modified-live preparation was IgG4/7 associated (13).…”

Impact of ETIF Deletion on Safety and Immunogenicity of Equine Herpesvirus Type 1-Vectored Vaccines

“…Immune responses against EHV-1 in horses, however, are characterized by high levels of EHV-specific IgA, identified as the predominant isotype upon natural EHV-1 infection (9). In agreement with these data we found that heterologous prime-boost regimens comprising subcutaneous priming with plasmid DNA and two nasal boosts with recombinant EHV-1 or EHV-⌬ETIF induced high levels of transgene-specific sIgA in BALB/c mice, as assessed with bronchoalveolar lavage (BAL) fluid.…”

“…Since the virus is absent in humans (40), it can be assumed that the problem of preexisting immunity should be of minor importance. Furthermore, EHV-1 infects a broad spectrum of different eukaryotic cells (50), and due to its ability to infect epithelial cells, EHV-1 challenge is characterized by strong mucosal immune responses (9). Due to these properties, EHV-1 strain RacH was selected recently as a novel vector for delivering vaccine genes into human cells (50,53).…”

“…This is most likely due to the virus's natural tropism for peripheral blood mononuclear cells (PBMCs), which play an important role in inducing innate and adapted immune responses (3,54). Above all, due to the virus's ability to infect epithelial cells, EHV-1 is characterized by inducing strong mucosal immune responses (9). Considering that distinct mucosal immune responses have been defined as one of the correlates of protective immunity against HIV (10,29), this represents an important feature for a vector system, not only for a potential HIV vaccine but also for diseases transmitted by the mucosal route in general.…”