Therapeutic evaluation of antibiotics combined with recombinant tuberculosis vaccine AEC/BC02 in a guinea pig model of Mycobacterium tuberculosis infection

Abstract

Objective To evaluate the therapeutic effect of antibiotics combined with recombinant tuberculosis vaccine AEC/BC02 on Mycobacterium tuberculosis infection in guinea pigs. Methods Two weeks after guinea pigs were challenged subcutaneously with a high dose of Mycobacterium tuberculosis, the guinea pigs with the positive skin test responses to the recombinant ESAT6-CFP10 allergen were randomly divided into four groups: normal saline (NS), AEC/BC02, antibiotics and antibiotics+ AEC/BC02.In antibiotics+ AEC/BC02 group, guinea pigs firstly received isoniazid (INH) and rifapentine (RFT) treatment once a week for a total of three times, and then were immunized with a single dose of AEC/BC02 vaccine six times at 10-day intervals.Guinea pigs in AEC/BC02 and antibiotics groups were respectively vaccinated with AEC/BC02 vaccine and given INH and RFT treatment at the same dose and frequency as given to antibiotics+ AEC/BC02 group.Thirteen weeks after challenge, all guinea pigs were sacrificed for necropsy. Results The gross pathological scores of NS, AEC/BC02, antibiotics and antibiotics+ AEC/BC02 groups were 83±8, 77±22, 45±28 and 19±14, respectively.Antibiotics+ AEC/BC02 group had a significantly lower gross pathological score than antibiotics, AEC/BC02 and NS groups (P<0.05, P<0.01, P<0.01, respectively). Moreover, the gross pathological scores of antibiotics and AEC/BC02 groups were significantly decreased as compared with that of NS group (both P<0.01). However, there was no significant difference between AEC/BC02 and NS groups.The spleen bacterial load of antibiotics+ AEC/BC02 group was (2.50±1.26) lg CFU, which was significantly lower than those of NS [(4.92+ 0.52) lg CFU], AEC/BC02 [(4.78+ 0.84) lg CFU] and antibiotics [(4.39+ 0.50) lg CFU] groups (P<0.01). Compared with NS group, antibiotic and AEC/BC02 groups showed no significant difference in spleen bacterial load.Histopathological changes indicated different levels of granulomatous lesions appeared in lung tissues of all groups and the most severe change was observed in AEC/BC02 group, followed by that in NS, antibiotics and antibiotics+ AEC/BC02 groups. Conclusion INH and RFT treatment in combination with AEC/BC02 vaccine in the treatment of guinea pigs with Mycobacterium tuberculosis infection was superior to either treatment alone as it significantly alleviated organ lesions and lowered the bacterial loads in spleen and lung. Key words: Antibiotics; Tuberculosis vaccine; Guinea pig; Combination; Protection