Effect of HIV status and retinol on immunogenicity to oral cholera vaccine in adult population living in an endemic area of Lukanga Swamps, Zambia

Abstract

Background We set out to assess the impact of human immunodeficiency virus (HIV) and micronutrient deficiency as indicated by serum retinol levels on the immune responses to Oral Cholera Vaccine (Shanchol™) in a cohort of participants in Lukanga Swamps, Zambia. Cholera remains endemic in Zambia with vaccines being the only effective preventive measures. However, the effect of these vaccines on populations living with HIV has not been widely documented. Methods HIV testing and confirmation was done using the Alere Determine™ HIV-1/2 and Uni-Gold™ kits while vibriocidal antibody assay was applied for vaccine immunogenicity. Serum retinol analysis was assessed by Shimadzu Prominence HCT-2010 High Performance Liquid Chromatography (HPLC). The primary outcome was log transformed geometric mean titre. Results From 47 participants screened for HIV, 51% (24) tested positive. There was a statistically significant reduction in Ogawa geometric mean ratio (GMR) by 67% (GMR = 0.33; 95% CI: -0.15, 0.76; p-value = 0.009) attributable to HIV positivity with a non-significant reduction in Inaba GMR by about 50% due to HIV positivity. When doubling of retinol levels modelled, GMR reduction against Ogawa were non-significant but that against Inaba resulted in a significant reduction in geometric mean titer (GMT) (GMT-0.33, C.I 0.16–0.66, p-value 0.002). At 1000copies/ml viral load cut off and 350 cells/μl CD4 counts, Ogawa GMT was two times higher 11.16 (95%CI: 8.20–15.19) versus 6.06 (95%CI: 4.04–9.10) in low viremia participants, and three times higher in above threshold CD4 count participants; 24.81 (95%CI: 18.94–32.50) versus 7.07 (95%CI: 5.22–9.58). Conclusion Our results show that while Shanchol™ is immunogenic in both HIV+/- individuals, HIV + participants responded poorly. Viral load and CD4 count affected vaccine immunogenicity. More research is required for detailed understanding of this in order to appropriately inform policy and practice.

Seroconversion and Kinetics of Vibriocidal Antibodies during the First 90 Days of Re-Vaccination with Oral Cholera Vaccine in an Endemic Population

“…Vibriocidal activity in both naïve and revaccinated adults living with HIV was also assessed, and found that, similar to the results previously reported [3], persons living with HIV had slightly lower titres when compared to their counterparts. These findings were similar to other studies [21].…”

“…Generally, vibriocidal antibody titers remain an indirect surrogate marker for longerterm immunity [14,15]. And in Zambia, the recently established vibriocidal assay is one of the reliable assays that is being used to measure cholera-specific antibodies in different scenarios [1][2][3][4]. Undoubtably, for the assessment of mucosal immunity, they certainly are a good proxy [16].…”

“…2 Piped/borehole/tube well from home or community. 3 Open pit latrine. 4 Covered pit latrine/flushing toilet.…”

“…Post the introduction of OCVs, studies have been conducted in cholera hotspot areas to assess its immunogenicity [1], delayed second dose regimen [2], its effect during HIV infection [3], and the effect of ABO blood types on OCV immunogenicity in vaccinated individuals [4]. However, there is limited information on the antibody kinetics in the first three months after re-vaccinating individuals resident in cholera hotspot areas.…”

“…Additionally, with global OCV shortages being experienced, there is an urgent need for each country reporting cholera outbreaks to be strategic on how vaccines are to be deployed, more-so with the recent introduction of the OCV single-dosing strategy. For instance, while a single-dose regimen has been employed in Zambia, the duration of protection remains questionable, with the high environmental enteric dysfunction (EED) [6] and HIV burden that can affect oral vaccine uptake [3].…”