Short communication
A randomised controlled trial of the immunogenicity and safety of a formaldehyde-inactivated Coxiella burnetii vaccine in 8-week-old goats

https://doi.org/10.1016/j.vetimm.2021.110253Get rights and content

Highlights

  • A formaldehyde-inactivated C. burnetii vaccine is immunogenic in 8-week-old goats.

  • Antibody titres induced by vaccinating 8-week-old goats were 4-fold over the cut-off.

  • Antibodies elicited by vaccinating 8-week-old goats persisted throughout study.

  • The vaccine was safe in 8-week-old goats, only inducing acceptable adverse reactions.

  • An immunohistochemistry assay was developed to detect C. burnetii antigen in tissue.

Abstract

Coxiella burnetii causes Q fever in individuals exposed to infected ruminants. Vaccination in 3−4-month-old goats, has been reported to result in significantly greater reduction in C. burnetii shedding compared to goats vaccinated one month before breeding, the most commonly used strategy of controlling Q fever on infected intensively-managed herds. It is possible that an even greater reduction in the number of animals shedding C. burnetii could be achieved if vaccination were administered shortly after protection from colostrum antibodies wanes and animals become susceptible to infection with C. burnetii. This study aimed to evaluate the immunogenicity and safety of a formaldehyde-inactivated phase 1 C. burnetii vaccine in 8-week-old goats. Two injections, four weeks apart, elicited specific IgM and IgG responses in all vaccinated goats (n = 6), while no antibodies were detected in two control groups (n = 12). Swelling at the site of inoculation was observed in all the vaccinated and in 10/11 of the placebo-treated goats but receded after 3 weeks. Weight change and rectal temperatures were also comparable between vaccinated and control goats. The data indicated that this vaccine could be suitable for immunising 8-week-old goats, although further trials to determine level of protection against challenge are required.

Introduction

Coxiella burnetii multiplies to extremely high numbers in ruminant placentas and consequently highly infectious loads may be shed in birth fluids, placenta and foetal membranes, posing a high risk of Q fever infection for susceptible humans (Roest et al., 2011a; Sánchez et al., 2006). Vaccination of ruminants with inactivated phase 1 C. burnetii antigen one month before breeding which has been shown to reduce C. burnetii shedding, is the most commonly used strategy of controlling C. burnetii on infected ruminant herds, as recommended by the manufacturers of the only existing livestock vaccine [Coxevac™, Ceva Sante Animale, France] (Astobiza et al., 2011a; Astobiza et al., 2011b; Eibach et al., 2012; Garcia-Ispierto et al., 2015; Guatteo et al., 2008; Hogerwerf et al., 2011; Piñero et al., 2014; Rousset et al., 2009; Taurel et al., 2014).

In contrast, a study that compared the efficacy of vaccinating 3 to 4-month-old goats to vaccination of goats one month before breeding, reported that those vaccinated at 3 to 4-months of age had a significantly greater reduction in the proportion of shedders and the amount of C. burnetii shed per animal compared to goats vaccinated one month before breeding (De Cremoux et al., 2012). The greater reduction in the proportion of shedders in goats vaccinated at 4-months of age than those vaccinated one month before breeding was likely due to the lower proportion of the 3 to 4-month-old animals already infected with C. burnetii at the time of vaccination.

Research on an infected intensive dairy enterprise in Victoria, Australia, revealed that snatch-reared goats fed 500 mL of pooled colostrum, started mounting IgM antibodies at around 9 weeks of age, shortly after maternally-derived colostrum antibodies had waned (Muleme et al., 2017a). This demonstrates that kid goats are susceptible and are being exposed to C. burnetii before 9 weeks of age (Muleme et al., 2017a). Prevention of infection and elimination of infection from herds, could be achieved if vaccination were administered shortly after protection from colostrum antibodies wanes and before animals lacking protective immunity are exposed to C. burnetii.

This study was therefore conducted to evaluate the immunogenicity and safety of a formaldehyde-inactivated phase 1 C. burnetii vaccine in 8-week-old goats. This is the first of planned studies aimed at investigating the possibility of achieving better C. burnetii vaccine effectiveness by vaccinating goats before they get infected. With efforts to import the only available livestock vaccine against C. burnetii (Coxevac) into Australia being unsuccessful owing to regulatory concerns (European Medicines Agency, 2010b), an autogenous formaldehyde inactivated vaccine for livestock against C. burnetii was developed and tested in 8-week-old goats as a pre-cursor study to planned field trials.

Section snippets

The vaccine and the placebo

A formaldehyde-inactivated vaccine was prepared by culturing, in specific-pathogen-free (SPF) chicken eggs, a C. burnetii isolate from an aborted goat foetus from a farm on a large dairy enterprise at the centre of a large Q fever outbreak (Bond et al., 2016). SPF embryonated chicken eggs that were 7 days old were inoculated with 0.1 mL of a C. burnetii (Meredith goat strain AuQ60) inoculum into the yolk sac. The eggs were incubated at 40 °C at 50 % humidity and candled every day to confirm

The vaccine and placebo

The final vaccine suspension had a concentration of 1.8 × 108C. burnetii per mL. The vaccine was free of both viable C. burnetii and residual formaldehyde as inoculation into VERO cell cultures resulted in absence of any cytopathogenic effect after 4 weeks of incubation. The vaccine passed the bacterial sterility test as no growth occurred on inoculation of the vaccine onto Horse Blood Agar after aerobic and anaerobic incubation for 72 h at 37 °C.

Immunogenicity of the vaccine in goats

The median age of the 18 goats at the time of

Funding

This research was funded by Meredith Dairy, the University of Melbourne and the Australian Rickettsial Reference Laboratory in Geelong.

Ethics approval

The culturing of C. burnetii in SPF eggs was approved by the Animal Care & Ethics Committee of the Australian Rickettsial Reference Laboratory, approval number ACEC/11. All procedures involving goats were undertaken in accordance with ethics application (ID 1413432) approved by The University of Melbourne Animal Ethics Committee.

Declaration of Competing Interest

The authors have no conflict of interest to declare.

Acknowledgements

The authors acknowledge considerable support provided from staff at the Asia-Pacific Centre for Animal Health at the University of Melbourne, the Australian Rickettsial Reference Laboratory and the Mackinnon Project, University of Melbourne. Particularly: Robin Geyer, Kirsten Bailey, Jose Canevari, Tabita Tan, Dianne Rees, Rhys Bushell, Andres Diaz, Jemima Amery-Gale, Nino Ficorilli, Helen Crabb, Carol Hartley and James Gilkerson.

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