ANTIBODY-MEDIATED PROTECTION AGAINST BRUCELLA-ABORTUS IN BALB C MICE AT SUCCESSIVE PERIODS AFTER INFECTION - VARIATION BETWEEN VIRULENT-STRAIN-2308 AND ATTENUATED VACCINE STRAIN-19/

In BALB/c mice antibodies specific for the O polysaccharide (OPS) as w ell as T lymphocytes mediate protective immunity to Brucella abortus. We performed quantitative analyses of isotypes of OPS antibodies gener ated during primary infections, and tested the protective qualities of antisera at successive stages of infection against B. abortus strain 2308, representative of the wild type, and attenuated vaccine strain 1 9. IgM antibodies predominated during the first 3-4 weeks of infection . IgG3 antibodies increased slowly for the first 3 weeks but then rose rapidly and persisted at high levels (> 300 mu g/ml). IgG1, IgG2a and IgG2b antibodies had increased slightly by week 3 and then remained a t low to moderate levels (< 70 mu g/ml). Week 2 serum pools (IgM high, IgG3 low or undetectable) transferred substantial protection against 2308 (greater than or equal to 1 log unit) which increased relatively little (to 1.2-1.5 log units) with later sera that were high in IgG an tibodies. In contrast, week 2 sera conferred low levels of protection against 19 (< 0.6 log units), but protection was dramatically increase d (to greater than or equal to 2.3 log units) with sera obtained 1 wee k later that had slightly increased Ige antibodies. Monoclonal IgM ant ibodies also provided better protection against 2308 than 19, while mo noclonal IgG3 antibodies protected much better against 19. Strain 19 o psonized with antibodies taken at any stage of infection was killed wi thin normal macrophages, whereas comparably opsonized 2308 underwent i ntracellular replication. Phagocytosis of 2308 was better than of 19 w hen brucellae were opsonized with either polyclonal IgM or IgG3 antibo dies, and the difference between strains was more extreme following Ig M opsonization. The data suggest an explanation for differences in the growth curves of 2308 and 19 in spleens of BALB/c mice. Higher number s achieved by 19 at week 2 could result from extracellular replication owing to ineffectual opsonization by IgM antibodies, while the precip itous decline of 19 beginning at week 3 could be caused by the increas e in more effective IgG3 opsonins that facilitate its rapid intracellu lar destruction.