TL;DR: In this article, the authors evaluated human immunity acquired after cholera or provided by choline vaccines and found that immunity, either naturally acquired or vaccine-induced, appeared to be directed against the vibrio rather than against the toxin.
Abstract: Human immunity acquired after cholera or provided by cholera vaccines was evaluated. Previous diarrhea caused by infection with Vibrio cholerae induced complete protection against diarrhea after a second challenge with the homologous organism four to 12 months later; vibrios were recovered from only one of 21 patients challenged with the homologous organism. Four of six other men challenged again after the same interval with a heterologous serotype developed mild diarrhea. A whole-cell Inaba vaccine, given either parenterally or orally, produced significant protection against excretion of the organisms and lowered the incidence and severity of diarrhea; the vaccine was more effective when administered parenterally. A partially purified toxoid vaccine also provided some protection. An individual's immunity either to infection or to diarrhea was not correlated with his serum titer of vibriocidal antibody or his serum titer of antitoxin. Immunity, either naturally acquired or vaccine-induced, appeared to be directed against the vibrio rather than against the toxin. At present, cholera vaccines are less effective than previous infection in prevention of subsequent illness.
TL;DR: The susceptibility of suckling mice to oral infection with several different Vibrio cholerae was determined and an Ogawa-derived ribosomal antigen was found to be superior to a commercial whole-cell vaccine or to purified cholera enterotoxin.
Abstract: The susceptibility of suckling mice to oral infection with several different Vibrio cholerae was determined. Mice up to 10 days of age were uniformly susceptible to oral infection with 10(8) colony-forming units of virulent organisms. Age-dependent resistance occurred thereafter to a maximum at about 15 days of age. The efficacy of selected vaccines was compared by oral challenge of 8-day-old, passively immunized CFW mice. An Ogawa-derived ribosomal antigen was found to be superior to a commercial whole-cell vaccine or to purified cholera enterotoxin. The ribosomal antigen was 50- to 100-fold more protective than the other vaccines on a weight basis against otherwise lethal challenge with Ogawa, Inaba, or El Tor Ogawa serotypes.
TL;DR: It was demonstrated that the live oral cholera vaccines did not remain viable in the intestine long enough to act antigenically.
Abstract: El Tor Ogawa C14-S5 and EW-6, two live vaccine candidate strains, were given to volunteers in varying doses with and without bicarbonate. Vibrios were found in the stool of one of 32 men given the vaccine strain, and only three men developed a significant titer rise (fourfold or greater) at 2 weeks of vibriocidal or antitoxic antibody. Five men who had previously received 109 organisms of the C14-S5 strain were challenged subsequently with virulent Ogawa 395 Vibrio cholerae. The rate of clinical infection in these men was no different than in unvaccinated controls. It was demonstrated that the live oral cholera vaccines did not remain viable in the intestine long enough to act antigenically.
TL;DR: A biological assay method using change in peripheral leukocyte population in mice as a response to toxic activity of endotoxin has been developed and there has been a fairly good correlation between the toxicity estimated and the pyrogenicity for rabbits with several kinds of biological products.
Abstract: A biological assay method using change in peripheral leukocyte population in mice as a response to toxic activity of endotoxin has been developed for quantitative determination of endotoxin. The method is relatively easy to perform, fairly precise and satisfactorily reproducible in estimation and sufficiently sensitive for detecting relatively small amounts. A particular advantage is that the assay can be completed within a few hours. There has been a fairly good correlation between the toxicity estimated by the method and the pyrogenicity for rabbits with several kinds of biological products. The relative toxicities of some bacterial vaccines were also estimated by the method.
TL;DR: Immunocytes releasing IgG antibody could be detected as readily as those immunocytes secreting IgM antibody in spleens of BALB/c mice and New Zealand White rabbits after a single injection of vaccine, and viable cholera vibrios were a more sensitive indicator cell in the immunoassay than sheep erythrocytes sensitized with a cellular extract from heated vibrio.
Abstract: The vibriolytic plaque-forming cell (PFC) assay was used to study the kinetics of the primary and secondary immune responses of mice and rabbits immunized with heat-killed cholera vibrios. Immunocytes releasing IgG antibody could be detected as readily as those immunocytes secreting IgM antibody in spleens of BALB/c mice and New Zealand White rabbits after a single injection of vaccine. Peak numbers of indirect (IgG) PFC were detected 3 to 4 days after the peak direct (IgM) PFC response (12 to 14 days). In contrast, only direct vibriolytic PFC were detected in spleens of NIH Albino mice during the primary response to cholera antigens. After a second injection of vaccine, IgM, IgG, and IgA PFC were detected in both mouse strains with peak responses for each immunocyte class occurring within the first week after booster injection. Heat-killed vibrios or a lipopolysaccharide (LPS) extract, but not cholera exotoxin or E. coli LPS, inhibited the vibriolytic response. Furthermore, viable cholera vibrios were a more sensitive indicator cell in the immunoassay than sheep erythrocytes sensitized with a cellular extract from heated vibrios.