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Chapter 25 : Induction of Serum Vibriocidal Antibodies by O-Specific Polysaccharide-Protein Conjugate Vaccines for Prevention of Cholera

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Abstract:

The experimental evidence to date indicates that the level of serum vibriocidal antibodies is correlated with the resistance of humans to cholera. This chapter proposes that a critical level of serum vibriocidal antibodies alone can prevent cholera, and describes a mechanism by which this may occur. On the basis of this hypothesis, vaccines have been designed to elicit antibodies, especially of the immunoglobulin G (IgG) class, to the lipopolysaccharide (LPS) of . The strongest evidence that serum vibriocidal antibodies may confer protective immunity comes from clinical studies of cholera vaccines composed of inactivated O1 (cellular vaccines). The authors have reconsidered the data that suggest that serum-neutralizing antibodies to cholera toxin (CT) (antitoxin) do not confer protection against cholera. As has been observed for many viral and bacterial diseases, serum antibodies are effective preventive but not therapeutic agents. This principle is probably also true for cholera. Clinical, epidemiologic, and experimental data support the hypothesis that serum vibriocidal antibodies confer protective immunity to cholera. The authors developed conjugate vaccines composed of the detoxified LPS of O1 serotype Inaba bound to CT that were designed to elicit protective levels of vibriocidal antibodies, especially in infants as part of their routine immunization. Cholera conjugate vaccines have the potential to elicit protection in infants when injected along with diphtheria-typhoid-pertussis vaccine and the type b conjugate as part of routine immunization.

Citation: Szu S, Robbins J, Gupta R. 1994. Induction of Serum Vibriocidal Antibodies by O-Specific Polysaccharide-Protein Conjugate Vaccines for Prevention of Cholera, p 381-394. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch25

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Figures

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Figure 1

13C NMR spectra () of V. cholerae O1 LPS, serotypes Inaba and Ogawa , recorded on a JEOL GSX-500 spectrometer. Approximately 10 mg of each LPS was dissolved in 0.5 ml of D2O and 1 µl of trimethylamine. The spectra were recorded at ambient probe temperature (ca. 20°C), and 40,000 free induction decay signals were averaged. Chemical shifts are relative to external sodium 3-(trimethylsilyl) propionate-2,2,3,3-d4.

Citation: Szu S, Robbins J, Gupta R. 1994. Induction of Serum Vibriocidal Antibodies by O-Specific Polysaccharide-Protein Conjugate Vaccines for Prevention of Cholera, p 381-394. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch25
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Image of Figure 2
Figure 2

31P NMR spectra () of V. cholerae O1 LPS serotypes Inaba and Ogawa , recorded on a JEOL GSX-500 spectrometer. Approximately 10 mg of each LPS was dissolved in 0.5 ml of D20 and 1 µ1 of trimethylamine and recorded at ambient probe temperature (20°C).

Citation: Szu S, Robbins J, Gupta R. 1994. Induction of Serum Vibriocidal Antibodies by O-Specific Polysaccharide-Protein Conjugate Vaccines for Prevention of Cholera, p 381-394. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch25
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Image of Figure 3
Figure 3

DeA-LPS was thiolated with SPDP and mixed with N-pyridyl dithio-derivatized protein. Cyanogen-derivatized DeA-LPS was linked with adipic acid dihydrazide. The hydrazide-derivatized polysaccharide was then linked to proteins in the presence of carbodiimide.

Citation: Szu S, Robbins J, Gupta R. 1994. Induction of Serum Vibriocidal Antibodies by O-Specific Polysaccharide-Protein Conjugate Vaccines for Prevention of Cholera, p 381-394. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch25
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Tables

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Table 1

Serum LPS antibodies elicited in mice by three injections of DeA-LPS-CT, LPS, or cellular cholera vaccines

Citation: Szu S, Robbins J, Gupta R. 1994. Induction of Serum Vibriocidal Antibodies by O-Specific Polysaccharide-Protein Conjugate Vaccines for Prevention of Cholera, p 381-394. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch25
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Table 2

Vibriocidal antibody titers of pooled sera from mice immunized with cholera conjugates, LPS, or cellular vaccines

Citation: Szu S, Robbins J, Gupta R. 1994. Induction of Serum Vibriocidal Antibodies by O-Specific Polysaccharide-Protein Conjugate Vaccines for Prevention of Cholera, p 381-394. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch25

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