Protection from clinical disease against three highly virulent strains of Newcastle disease virus after in ovo application of an antibody-antigen complex vaccine in maternal antibody-positive chickens.

Worldwide, Newcastle disease (ND) remains one of the most economically important diseases of poultry. Current vaccination strategies for commercial poultry include the use of inactivated and live ND vaccines that typically induce protection against virulent field viruses. Here, we tested the efficacy of an antigen-antibody complex (AAC) ND vaccine delivered in ovo. Commercial maternal antibody-positive broiler chickens (Gallus domesticus) were vaccinated in ovo with an AAC vaccine composed of live B1-LaSota Newcastle disease virus (NDV) complexed with NDV-specific antiserum, and then they were challenged at weekly intervals after hatch. Challenge viruses included three exotic ND disease (END) viruses: the neurotropic strain Texas GB NDV-92-01 (TxGB) and two viscerotropic isolates, one isolate from the 2002-2003 outbreak in California (California 2002 isolate S212676 [CA]) and the other isolate from a 1997 END outbreak in South Korea (South Korea 94-147 [SK]). Results demonstrate that maternal antibody was able to provide approximately 50% protection in either vaccinated or control chickens at 7 days of age after TxGB challenge. However, with challenge at > or = 14 days, most control birds died, whereas all AAC-vaccinated birds were protected. Challenge with the CA or SK viruses in chickens at 28 days of age resulted in 100% protection of vaccinated birds, whereas all control birds died. In addition, AAC-vaccinated birds displayed decreased incidence of viral shedding in oral and cloacal swabs than control birds. Antibody titers were significantly (P < 0.05) higher in vaccinated chickens, as determined by enzyme-linked immunosorbent assay and hemagglutinin-inhibition tests, than in nonvaccinated controls. Together, these results demonstrate the efficacy of AAC vaccines delivered in ovo to protect commercial poultry.

Optimized adenovirus-antibody complexes stimulate strong cellular and humoral immune responses against an encoded antigen in naive mice and those with preexisting immunity.

The immune response to recombinant adenoviruses is the most significant impediment to their clinical use for immunization. We test the hypothesis that specific virus-antibody combinations dictate the type of immune response generated against the adenovirus and its transgene cassette under certain physiological conditions while minimizing vector-induced toxicity. In vitro and in vivo assays were used to characterize the transduction efficiency, the T and B cell responses to the encoded transgene, and the toxicity of 1 × 10(11) adenovirus particles mixed with different concentrations of neutralizing antibodies. Complexes formed at concentrations of 500 to 0.05 times the 50% neutralizing dose (ND(50)) elicited strong virus- and transgene-specific T cell responses. The 0.05-ND(50) formulation elicited measurable anti-transgene antibodies that were similar to those of virus alone (P = 0.07). This preparation also elicited very strong transgene-specific memory T cell responses (28.6 ± 5.2% proliferation versus 7.7 ± 1.4% for virus alone). Preexisting immunity significantly reduced all responses elicited by these formulations. Although lower concentrations (0.005 and 0.0005 ND(50)) of antibody did not improve cellular and humoral responses in naïve animals, they did promote strong cellular (0.005 ND(50)) and humoral (0.0005 ND(50)) responses in mice with preexisting immunity. Some virus-antibody complexes may improve the potency of adenovirus-based vaccines in naïve individuals, while others can sway the immune response in those with preexisting immunity. Additional studies with these and other virus-antibody ratios may be useful to predict and model the type of immune responses generated against a transgene in those with different levels of exposure to adenovirus.