Coxiella burnetii, the agent responsible for Q Fever, exists in two antigenic forms: the LPS in the bacterial wall of phase I strains has a more complete antigenic structure than the LPS of phase II strains. Phase I strains are therefore more infectious and induce a more complete immune response. However, it is important to note that phase II antigens are present on all strains, whatever their phase. In other words, it can be said that phase II strains have a partially truncated antigenic structure compared with phase I strains.
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A complex humoral and cellular immunity
As all infectious diseases, the humoral response begins with the production of IgM. Later, IgG begins to be synthesised and the circulation of IgM gradually decreases. In the case of Q Fever, another factor must also be taken into account: anti-phase II antibodies and anti-phase I antibodies. Anti-phase II antibodies are the first to be produced by B lymphocytes, while anti-phase I antibodies appear later. This temporal difference is not fully explained, but one hypothesis is that the immune system has better access to phase II antigens (Bauer et al., 2021).
The kinetics of the immune response have been studied in goats (Roest et al., 2013, Muleme et al., 2017). Anti-phase II IgM and anti-phase II IgG appear first. Their synthesis starts 2 weeks after infection. Circulating IgM levels fall after 4 to 6 weeks, while IgG levels are maintained for longer. Anti-phase I antibodies appear later: in the case of IgM, a first peak of moderate amplitude is observed around 4 weeks after infection, and a second, more significant peak around 6 weeks. Levels then fall from 7 weeks onwards. Anti-phase I IgG production starts at around 6 weeks and persists over time. The decrease in anti-phase II antibodies could explain the transition of the disease into a chronic phase (Muleme et al., 2017). Cellular immunity is assessed by measuring interferon gamma (IFN gamma). In Roest's study, interferon production in goats began around 6 weeks after infection, was maintained for around 5 weeks and then declined. This seems to indicate that cellular immunity comes into play during a new infection, but not in the case of a chronic infection.
In cattle, in a study published in 2017, Boettcher compared the level of gamma interferon, antibodies against phase I and antibodies against phase 2. Cattle with chronic disease had only antibodies against phase I whereas cows with acute disease (such as abortion) had both interferon and antibodies. This study also highlighted that in the case of acute disease, antibodies are directed against phase II Coxiella burnetii whereas they are against phase I in chronic disease (Boettcher et al., 2017).
Immune response triggered by vaccination
In experimental studies in rodents, it has been shown that immunization with a phase I vaccine triggers both cellular immunity and humoral immunity and provide a good protection against different isolates of Coxiella burnetti (Zhang and Samuel, 2004; Kersh et al., 2013). It was also showed that in contrast to phase II vaccines, phase I are able to trigger a full humoral immunity with the production of antibodies against both phase II and phase I bacteria.
The Ceva’s vaccine against Q Fever in ruminants, is a Coxiella burnetii phase I inactivated and non-adjuvanted vaccine. These two characteristics make it very safe but, one could fear a low cellular immune response because of the absence of adjuvant. However, an experimental study in sheep (Bauer et al., 2023) showed that although the production of IFN-gamma triggered by the primary vaccination was low, the booster vaccination led to a significant increase in the cellular immune response. It can therefore be said that similar to the experimental studies in rodents, vaccination of ruminants with Ceva’s vaccine stimulates both the humoral and the cellular immunity pathways.
References
Bauer, B. U., Knittler, M. R., Prüfer, T. L., Wolf, A., Matthiesen, S., Runge, M., & Ganter, M. (2021). Humoral immune response to Q fever vaccination of three sheep flocks naturally pre-infected with Coxiella burnetii. Vaccine, 39(10), 1499-1507.
Bauer, B. U., Schwecht, K. M., Jahnke, R., Matthiesen, S., Ganter, M., & Knittler, M. R. (2023). Humoral and cellular immune responses in sheep following administration of different doses of an inactivated phase I vaccine against Coxiella burnetii. Vaccine, 41(33), 4798-4807.
Boettcher, J., Schumacher, M., Motsch, B., Mehne, D., Alex,.M, et al. (2017) Feasibility Study on Coxiella burnetii Phase-Specific Antibody Tests and Interferon-γ-Recall Assay in Dairy Cattle. J Vet Med Res 4(9): 1106.
Kersh, G. J., Fitzpatrick, K. A., Self, J. S., Biggerstaff, B. J., & Massung, R. F. (2013). Long-Term immune responses to Coxiella burnetii after vaccination. Clinical and Vaccine Immunology, 20(2), 129-133.
Muleme, M., Campbell, A., Stenos, J., Devlin, J. M., Vincent, G., Cameron, A., ... & Firestone, S. (2017). A longitudinal study of serological responses to Coxiella burnetii and shedding at kidding among intensively-managed goats supports early use of vaccines. Veterinary research, 48, 1-15.
Roest, H. I., Post, J., van Gelderen, B., van Zijderveld, F. G., & Rebel, J. M. (2013). Q fever in pregnant goats: humoral and cellular immune responses. Veterinary research, 44, 1-9.
Zhang, G., & Samuel, J. E. (2004). Vaccines against Coxiella infection. Expert review of vaccines, 3(5), 577-584.
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