Antibody and cytokine responses of koalas (Phascolarctos cinereus) vaccinated with recombinant chlamydial major outer membrane protein (MOMP) with two different adjuvants
Khan, SA, Desclozeaux, M, Waugh, C, Hanger, J, Loader, J, Gerdts, V, Potter, A, Polkinghorne, A, Beagley, K & Timms, P 2016, PLoS ONE, vol. 11, no. 5, e0156094.
Two different adjuvants used in an anti-chlamydial recombinant major outer membrane protein (rMOMP) antigen-based vaccine for koalas both induced strong antigen-specific cellular responses and were equally able to produce Chlamydia pecorum-specific neutralising antibodies in vitro. The adjuvants differed in terms of the specificity of the MOMP epitope antibodies produced.
A vaccine consists of an antigen, which elicits an immune response, and an adjuvant, which is added to enhance and, in some cases, modify the immune response elicited by the antigen. This work built upon prior studies which found that a two- to three-dose regimen of an rMOMP antigen-based vaccine adjuvanted with immune stimulating complex (ISC) and a single-dose rMOMP antigen-based vaccine adjuvanted with polyinosinic-polycytidylic acid (poly I:C), polyphosphazine (PCEP) and host defence peptides (HDPs) (tri-adjuvant) both produced strong cellular and humoral immune responses against C. pecorum infection in small populations of captive koalas. This study sought to further examine the effects of these two adjuvants on antibody and cytokine responses following vaccination. Koala subjects from the same wild population were divided into two groups and each group vaccinated with the rMOMP antigen adjuvanted with either the ISC or tri-adjuvant formula. Both adjuvants performed similarly at inducing an antigen-specific cellular response, though the tri-adjuvant was produced a slightly higher interferon gamma (IFN-ү) and interleukin IL-17A (IL-17A) response. These are both important cytokines for protection against chlamydial infection. On the other hand, the ISC adjuvant resulted in slightly higher plasma Immunoglobin G titres than the tri-adjuvant formula. The adjuvants were equal in terms of their C. pecorum-specific neutralising antibody potential. The epitopes (the part of the antigen that is recognised by the immune system) targeted by the antibodies in the plasma were identified and differed as a result of each adjuvant. Koalas in the ISC-immunised cohort recognised three C. pecorum MOMP peptides whereas those that received the tri-adjuvant formulation recognised an additional two. Most of these anti-epitope antibodies contributed to infection neutralisation in vitro.
Chlamydia is one of the greatest threats to the viability of koala populations, and therefore the development of an effective vaccine that can be feasibly implemented on a broad scale is a key priority in the conservation of the species. While the ISC-based vaccine is not ideal for use in a vaccination program in wild koalas due to the difficulty of coordinating multiple immunisation events for an animal, preliminary evidence has suggested that the preferable one-dose tri-adjuvant formulation is safe for use in koalas.
This study demonstrated that both adjuvants were comparable in terms of the immune response induced to the rMOMP antigen, which suggests that the preferred single-dose tri-adjuvant may be equally as effective as the three-dose ISC-based vaccine. The identification of the epitopes that contribute most significantly to infection neutralisation is also beneficial for future vaccine development and evaluation. Further research will be required to determine the longevity of the immune response elicited by each vaccine formulation.
Summarised by Joanna Horsfall
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