An Age-stratified, Randomized Immunogenicity Trial of Killed Oral Cholera Vaccine with Delayed Second Dose in Cameroon

Abstract

ABSTRACT. The recommended schedule for killed oral cholera vaccine (OCV) is two doses, 2 weeks apart. However, during vaccine campaigns, the second round is often delayed by several months. Because more information is needed to document antibody responses when the second dose is delayed, we conducted an open-label, phase 2, noninferiority clinical trial of OCV. One hundred eighty-six participants were randomized into three dose-interval groups (DIGs) to receive the second dose 2 weeks, 6 months, or 11.5 months after the first dose. The DIGs were stratified into three age strata: 1 to 4, 5 to 14, and > 14 years. Inaba and Ogawa vibriocidal titers were assessed before and after vaccination. The primary analysis was geometric mean titer (GMT) 2 weeks after the second dose. Data for primary analysis was available from 147 participants (54, 44, and 49 participants from the three DIGs respectively). Relative to the 2-week interval, groups receiving a delayed second dose had significantly higher GMTs after the second dose. Two weeks after the second dose, Inaba GMTs were 55.1 190.3, and 289.8 and Ogawa GMTs were 70.4, 134.5, and 302.4 for the three DIGs respectively. The elevated titers were brief, returning to lower levels within 3 months. We conclude that when the second dose of killed oral cholera vaccine was given after 6 or 11.5 months, vibriocidal titers were higher than when given after the standard period of 2 weeks. This provides reassurance that a delayed second dose does not compromise, but rather enhances, the serological response to the vaccine.

Effectiveness of one dose of killed oral cholera vaccine in an endemic community in the Democratic Republic of the Congo: A matched case-control study

“…Finally, we were unable to obtain reliable estimates of two dose protection partly because few cases reported receipt of two doses of kOCV due to low vaccination coverage in the population, and potentially because of uncertainty in the reporting of more than one dose of kOCV (Tables S3 and S4). Our findings, combined with data from dose-interval studies conducted in Cameroon and Zambia 36,37 , suggest that providing a second dose a year or more after the first could lead to better and longer lasting protection against cholera than the current two-dose series, at least among older children and adults. While more data are needed across different settings and for longer periods of time, our study extends the current evidence base on protection from a singledose of kOCV, and more specifically on protection from Euvichol-Plus, the most widely used cholera vaccine available today.…”

“…Our findings, combined with data from dose-interval studies conducted in Cameroon and Zambia 35,36 , suggest that providing a second dose a year or more after the first could lead to better and longer lasting protection against cholera than the current two-dose series, at least among older children and adults. While more data are needed across different settings and for longer periods of time, our study extends the current evidence base on protection from a singledose of kOCV, and more specifically on protection from Euvichol-Plus ® , the most widely used cholera vaccine available today.…”

Effectiveness of one dose of killed oral cholera vaccine in an endemic community in the Democratic Republic of the Congo: a matched case-control study

“…Data from dose-interval studies conducted in Cameroon and Zambia, 35 , 36 suggest that providing a second dose of kOCV a year or more after the first dose could lead to better and longer lasting protection against cholera than the current two-dose regimen, at least among individuals older than 5 years. Although more data are needed across different settings and for longer periods of time, our study extends the current evidence base on the protection of a single dose of kOCV, and, more specifically, on the protection of Euvichol-Plus, the most widely used cholera vaccine available today.…”