Immunoglobulin A as an Early Humoral Responder After Mucosal Avian Coronavirus Vaccination

Abstract

Infectious bronchitis virus (IBV) is a highly contagious coronavirus prevalent in all countries with an extensive poultry industry and continues to cause economic losses. IBV strains of the Ark serotype are highly prevalent in the Southeastern United States despite extensive vaccination. One explanation for this observation is the high genetic variability of IBV. In addition, IBV Ark-type vaccines may induce suboptimal mucosal immune responses, contributing to the prevalence and persistence of the Ark serotype. To test this hypothesis, chickens were ocularly vaccinated with a commercially available live attenuated IBV Ark-Delmarva Poultry Industry vaccine strain and both mucosal and systemic antibody responses were measured. The highest immunoglobulin A (IgA) spot-forming cell (SFC) response was observed in the Harderian glands (HG) and to a lesser extent in the spleen and conjunctiva-associated lymphoid tissues, while a limited IgG SFC response was observed in either the mucosal or systemic immune compartment. Interestingly, the peak IgA SFC response occurred 2 days earlier in spleen than in the head-associated lymphoid tissues despite ocular vaccination. Furthermore, IgA IBV-specific antibody levels significantly increased over controls 3 days earlier in tears and 4 days earlier in plasma than did IgG antibodies. IgA antibody levels were higher than IgG antibody levels throughout the primary response in tears and were similar in magnitude in plasma. In addition, a very early increase in IgA antibodies on day 3 postvaccination was observed in tears; such a response was not observed in plasma. This early increase is consistent with a mucosal T-independent IgA response to IBV. In the secondary response the IBV antibody levels significantly increased over controls starting on day 1 after boosting, and the IgG antibody levels were higher than the IgA antibody levels in both tears and plasma. In summary, ocular vaccination induced higher IgA antibodies in the primary IBV response, while the memory response is dominated by IgG antibodies. Thus, lower mucosal IgA antibody levels are observed upon secondary exposure to IBV, which may contribute to vulnerability of host epithelial cells to infection by IBV and persistence of the Ark serotype.

Age-dependent immune responses and immune protection after avian coronavirus vaccination

“…IBV propagation and purification for ELISA: IBV was propagated in SPF White Leghorn embryonated chicken eggs (Sunrise Farms, Inc., Catskills, NY) by inoculation on day 10 of embryonation as previously reported [20]. Supernatants were titrated for the IBV virus using the Reed and Muench method [21].…”

Immune Responses to Virulent and Vaccine Strains of Infectious Bronchitis Viruses in Chickens

“…This was also supported by a study that showed a significant correlation between the levels of lachrymal anti-IBV IgG at 5 dpi in chickens vaccinated with the full dose of H120 and tracheal protection against homologous IBV challenge (78). In addition, a recent study also corroborates this hypothesis, which reported that secondary antibody response at mucosal sites (lachrymal secretion) induced by attenuated IBV vaccines are dominated by an early and high production of anti-IBV IgG in re-immunized chickens (80).…”

“…A recent study demonstrated that ocular vaccination with live attenuated Ark IBV vaccine induced higher IgA antibodies (in lachrymal fluid and plasma) in the primary IBV response, while the memory response is dominated by IgG antibodies. Therefore, lower mucosal IgA antibody levels are observed upon secondary exposure to IBV, which may contribute to increased susceptibility of host epithelial cells to reinfection by IBV and the persistence of the Ark serotype (80).…”

Topical Administration Is a Promising Inoculating Route versus Intramuscular Inoculation for the Nanoparticle-Carried DNA Vaccine to Prevent Corneal Infections

“…Our results show that with the aid of the nanoparticles, the inoculation route of the DNA vaccine is still the key factor for its efficacy. Although the topical inoculation and intramuscular inoculation of the nanoparticle-carried vaccine generated similar systemic immune responses (the specific proliferative and cytotoxic activities of the splenic lymphocytes, cytokine levels and anti-HSV-1 neutralizing antibodies), topical inoculation produced significantly higher levels of local sIgA than intramuscular inoculation, and this local mucosal immune reaction may play a key role in defending against HSV local corneal infection [23]; our clinical data verify this: the keratitis degree after topical inoculation of nanoparticle-carried vaccine was significantly decreased compared to keratitis after intramuscular inoculation. Furthermore, topical inoculation of vaccine alone (without nanoparticles) also showed significantly higher local sIgA levels and consequently decreased the keratitis degree as compared to the intramuscular inoculation of nanoparticle-carried DNA vaccine.…”

“…On the ocular surface, there is the same mucosa-associated lymphoid tissue as in other mucosal tissues, which is called ocular mucosal immune system, through which foreign antigens invading the ocular surface can be presented locally, further stimulating B cells and T cells, resulting in ocular specific cellular and humoral immune responses, such as secreting high levels of secretory immunoglobulin A (sIgA) [23,24,25,26,27]. Corneal infection is exactly such a kind of ocular mucosal infection, and we hypothesized that topical (mucosal) inoculation of DNA vaccine can generate stronger specific local immune responses than systemic intramuscular inoculation to protect corneal infections.…”