Safety and immunogenicity in human volunteers of a chloroform-methanol residue vaccine for Q fever

Abstract

Current Q fever vaccines, consisting of Formalin-inactivated phase I whole CoxieUa burnetii, are highly efficacious in preventing disease in high-risk settings but are associated with a risk of unacceptable local reactions in previously immune individuals and require cumbersome preliminary immunologic evaluation of potential vaccinees. A vaccine prepared from the residue of chloroform-methanol extraction of phase I Henzerling strain C. burnetii (CMR) has been shown to be less reactogenic but still immunogenic and protective in small animals and sheep. In a placebo-controlled trial, we immunized 35 healthy adults unscreened for markers of prior C. burnetii immunity with a single subcutaneous CMR dose of 30, 60, 120, or 240 jg. None of those receiving the 30or 60-jig CMR dose and none of the placebo recipients experienced any adverse effects. Five of 15 120-jig dose CMR recipients complained of transient discomfort in the inoculated arm; erythema or induration of 2100 mm2 was noted in three and four, respectively, and two had malaise and low-grade fever (<101F, orally). No 240pg dose vaccinee reported limb discomfort, but 7 of 10 had erythema and/or induration of .100 mm2 (p < 0.001 versus placebo). Two reported malaise, and one had low-grade fever. All adverse effects were self-limited. Serum immunoglobulin M responses were optimally detected with CMR antigen and occurred in 50, 60, 73, and 90% of recipients of the 30-, 60-, 120-, and 240-jg doses, respectively; results with phase I whole-cell antigen were similar. Serum immunoglobulin G responses were best detected with phase II antigen and were seen in 20, 20, and 40%o of those receiving the 60-, 120-, and 240-jig doses, respectively. Peripheral blood T-cell proliferative responses to C. burnetii recall antigens were transient and of low magnitude but were seen with CMR antigen in 33% of 120-pg dose recipients and 40% of 240-jg dose recipients. Data from this study and those from comparative-efficacy trials in primates should provide the basis for field trials of the CMR vaccine.

The Effectiveness of Coxiella burnetii Vaccines in Occupationally Exposed Populations: A Systematic Review and Meta‐Analysis

“…Multiple outcomes were reported to evaluate the effect of a given vaccine on the study population. Antibody assays to evaluate post‐vaccination seroconversion included complement fixation (CF) ( n = 12) (Meiklejohn and Lennette, ; Luoto et al., ; Vivona et al., ; Sterkhova, ; Genig and Gamelaya, ; Morris et al., ; Kazar et al., ; Ascher et al., ; Worswick and Marmion, ; Izzo et al., ; Krutitskaya et al., ), immunofluorescence (IF) ( n = 3) (Ascher et al., ; Worswick and Marmion, ; Krutitskaya et al., ), microagglutination (MA) ( n = 5) (Luoto et al., ; Bell et al., ,b; Kazar et al., , , ) and ELISA ( n = 3) (Fries et al., ; Krutitskaya et al., ; Camacho et al., ). However, there was limited consistency in assay preparation, sensitivity, specificity or cut‐off interpretation.…”

“…However, there was limited consistency in assay preparation, sensitivity, specificity or cut‐off interpretation. Whole blood evaluations of cell‐mediated immunity (CMI) to C. burnetii were measured by in vitro proliferative responses of peripheral lymphocytes to multiple mitogens ( n = 5) (Ascher et al., ; Izzo et al., ; Gajdozova and Brezina, ; Fries et al., ; Waag et al., ). Delayed‐type hypersensitivity was used as a proxy measure of CMI in one study (Kazar et al., ).…”

Protective Immunity against Q Fever Induced with a Recombinant P1 Antigen Fused with HspB of Coxiella burnetii

“…The present vaccines to Q fever available were composed of either formalinkilled whole C. burnetii cells (WCbs) or chloroform-methanol residue of C. burnetii cells (CMRs). 4,5 WCbs' protective ability is well documented, but the adverse reactions induced by WCb vaccine, including fever, anorexia, malaise and tenderness, erythema, and edema at the inoculation site, are also well documented. 4,6 Although CMR vaccines are shown to be better tolerated in animals than WCb vaccine, 7 largescale culture and purification of C. burnetii and preparation of CMR vaccine are time-consuming, labored, and even hazardous.…”

Scientific Opinion on Q fever

“…a. Vaccination Current vaccines used in humans and animals include formalin-killed, whole-cell vaccine preparations (WCV) (Marmion et al, 1990) and chloroform methanol-extracted bacterial residue (CMR) (Williams et al, , 1992Fries et al, 1993;Waag et al, 1997). The two types of vaccines (WCV and CMR) protect monkeys (Macaca fascicularis) against fever and bacteriemia after challenge with an aerosol (Waag et al, 2002).…”