A single dose of live oral cholera vaccine CVD 103-HgR is safe and immunogenic in HIV-infected and HIV-noninfected adults in Mali

Abstract

Despite considerable experience with single-dose, live, oral cholera vaccine CVD 103-HgR in Asia, Europe, and the Americas, the vaccine had not been evaluated in sub-Saharan Africa or on individuals infected with human immunodeficiency virus (HIV). We therefore conducted a randomized, placebo-controlled, double-blind, cross-over clinical trial in 38 HIV-seropositive (without clinical acquired immunodeficiency syndrome (AIDS)) and 387 HIV-seronegative adults in Mali to assess its safety and immunogenicity. Adverse reactions (fever, diarrhoea and vomiting) were observed with similar frequency among vaccine and placebo recipients. The vaccine strain was not isolated from the coprocultures of any subject. The baseline geometric mean titre (GMT) of serum vibriocidal antibody was significantly lower in HIV-seropositives (1:23) than in HIV-seronegatives (1:65) (P = 0.002). Significant rises in vibriocidal antibody were observed in 71% of HIV-seronegatives and 58% of HIV-seropositives, and in 40% of HIV-seropositives with CD4+ counts below 500 per microliter. Following immunization, the peak vibriocidal GMT in HIV-seronegatives was 1:584 versus 1:124 in HIV-seropositives (P = 0.0006); in HIV-seropositives with CD4+ counts < 500 per microliter, the peak vibriocidal GMT was 1:40 (P = 0.03 versus other HIV-seropositives). CVD 103-HgR was safe in HIV-infected Malian adults, although serological responses were significantly attenuated among HIV-seropositives (particularly in those with CD4+ counts < 500 per microliter) relative to HIV-seronegatives. These results encourage further evaluations of this single-dose, oral cholera vaccine in high-risk populations such as refugees in sub-Saharan Africa.

PIP: In response to the 1994 cholera outbreak that swept through Rwandan refugee camps near Goma, Zaire, in 1994, the World Health Organization explored the immunogenicity of a new generation of single-dose, live oral cholera vaccines. One such vaccine, CVD 103-HgR, has been evaluated in Asia, Europe, and the Americas, but not in sub-Saharan Africa or in individuals infected with HIV. Therefore, the present study evaluated the safety and immunogenicity of this new vaccine in a randomized, placebo-controlled, double-blind, crossover clinical trial in Mali. Enrolled were 38 HIV-positive individuals without full-blown AIDS and 387 HIV-negative adults. Adverse reactions (fever, diarrhea, and vomiting) occurred with equal frequency in vaccine and placebo recipients. The vaccine strain was not isolated from the coprocultures of any subject. The baseline geometric mean titre (GMT) of serum vibriocidal antibody was significantly lower in HIV-positive subjects (1:23) than HIV-negatives (1:65). Significant rises in vibriocidal antibody were observed in 71% of HIV-seronegatives and 58% of HIV-positives and in 40% of HIV-positives with CD4 counts below 500/mcl. After immunization, the peak vibriocidal GMT in HIV-negative subjects was 1:584 compared with 1:124 in HIV-positive subjects. In HIV-positives with a CD4 count below 500/mcl, the peak vibriocidal GMT was 1:40. Although serologic responses were significantly attenuated among HIV-positive subjects, especially those with CD4 counts below 500/mcl, CVD 103-HgR was safe in HIV-infected Malian adults. Further evaluations of this single-dose oral cholera vaccine are recommended in high-risk populations such as refugees in sub-Saharan Africa.