IMMUNE-COMPLEX VACCINES: room for improvement?

The advantages of the use of immune-complex vaccines against Gumboro disease had already been discovered in the 1990s.

Different researchers demonstrated that the IBD immune-complex vaccines, prepared by combining a live attenuated vaccine strain with specific antibodies to IBDV, were able to overcome the common threat of the inactivation of the vaccine virus by passive antibodies, offering the possibility of administering these vaccines in-ovo or subcutaneously on the first day of life.

FIGURE 1: IBDV completely coated with specific antibodies (IgY)


In addition, the use of IBD immune-complex vaccines has also been related to improved safety (less lymphoid depletion and higher repopulation of B lymphocytes in the bursa; avoiding risk of virus replication in the bursa during the first week of life) and increased potential for humoral response compared to the use of the vaccine virus (antigen) alone1,2.

The main goal of this type of vaccine is, then, to provide enough protection for the vaccine virus (to avoid neutralization or safety issues) by ensuring that it is completely coated with IBDV-specific antibodies (see Figure 1 above).

How are immune-complex vaccines formulated? Is this coating being controlled?

All immune-complex vaccines against IBDV are formulated on the basis of adding a specific proportion of antibodies, depending on the initial titre of the vaccine harvest (Figure 2).

FIGURE 2: Formulation basis of IBDV immune-complex vaccines. Although the main objective of the process is to ensure the potency and safety of the vaccine with a completely coated virus, the final controls implemented do not guarantee that.


This initial titre is commonly determined on the titration substrate such as embryonated hens’ eggs (EID50: egg or embryo infective dose 50%) or cell lines (TCID50: tissue culture infective dose 50%) in a similar way to the titration performed with conventional live vaccines.

Once the IBDV-specific antibody has been added, the mixture will go through a freeze-drying process, which may induce some titre losses.

Some immune-complex vaccines show this virus titration and serum quantity before freeze-drying in their technical specifications, which does not take into account the possible titre loss during the process or the correct coating of the virus particles.

Others perform indirect titrations after freeze-drying based on an IBDV ELISA test in specific pathogen-free (SPF) birds (CID50: Chicken Infective dose 50%), which may take into account the possible loss of titre, but again this does not ensure that all virus particles are coated with specific antibodies (the goal of the immune-complex vaccines).



1Whitfill et al. 1995. Avian Diseases 39, 4, 687-699.
2Jeuriseen et al. 1998. Immunology 95, 494–500.