The Effect of Smallpox and Bacillus Calmette-Guérin Vaccination on the Risk of Human Immunodeficiency Virus-1 Infection in Guinea-Bissau and Denmark

Abstract

BackgroundThe live smallpox and Bacillus Calmette-Guérin (BCG) vaccinations have been associated with better adult survival in both Guinea-Bissau and Denmark. In Guinea-Bissau, human immunodeficiency virus (HIV)-1 became an important cause of death after smallpox vaccination was phased out globally in 1980. We hypothesised that smallpox and BCG vaccinations were associated with a lower prevalence of HIV-1 infection, and we tested this hypothesis in both Guinea-Bissau and Denmark.MethodsWe conducted 2 studies: (1) a cross-sectional study of HIV infection and vaccination scars in Guinea-Bissau including 1751 individuals and (2) a case-base study with a background population of 46239 individuals in Denmark. In Guinea-Bissau, HIV-1 transmission was almost exclusively sexually transmitted. In Denmark, we excluded intravenous drug users. Data were analyzed using logistic regression.ResultsBacillus Calmette-Guérin and/or smallpox vaccination compared with neither of these vaccines was associated with an adjusted odds ratio (aOR) for HIV-1 of 0.62 (95% confidence interval [CI], 0.36–1.07) in Guinea-Bissau and 0.70 (95% CI, 0.43–1.15) in Denmark. We combined the results from both settings in a meta-analysis (aOR = 0.66; 95% CI, 0.46–0.96). Data from Guinea-Bissau indicated a stronger effect of multiple smallpox vaccination scars (aOR = 0.27; 95% CI, 0.10–0.75) as follows: women, aOR = 0.18 (95% CI, 0.05–0.64); men, aOR = 0.52 (95% CI, 0.12–2.33); sex-differential effect, P = .29.ConclusionsThe studies from Guinea-Bissau and Denmark, 2 very different settings, both suggest that the BCG and smallpox vaccines could be associated with a decreased risk of sexually transmitted HIV-1. It might be informative to pursue this observation and explore possible protective mechanisms as part of the search for an HIV-1 vaccine.

Phase-out of smallpox vaccination and the female/male HIV-1 prevalence ratio: an ecological study from Guinea-Bissau

“…It has been reported that smallpox vaccination reduced susceptibility to unrelated infectious diseases,1 and in immunological in vitro studies, smallpox vaccination was associated with an up to fivefold reduction in C-C chemokine receptor 5 (CCR5) tropic HIV-1 replication 2. Based on vaccination scar readings in Guinea-Bissau and school health records in Denmark, we have shown that smallpox vaccination (and BCG) was associated with a lower risk of HIV-1 3. The adjusted OR for HIV-1 infection was 0.52 (95% CI 0.32 to 0.84) for women and 0.77 (95% CI 0.48 to 1.24) for men.…”

“…Estimated smallpox vaccination scar prevalence in different age groups for each sequential HIV survey. Based on data from Bissau, Guinea-Bissau, previously published 6. The estimation for the age group ≥35 in 2016 was changed to ≥45 to ensure a steady smallpox vaccination coverage.…”

“…As this study was based on previously published data,4–6 neither patients or the public were involved in conducting this research.…”

“…Smallpox vaccination typically leaves a distinct vaccination scar. We used a cohort of individuals, who had both participated in a smallpox vaccination scar survey (2005–2007) and an HIV prevalence survey (2004–2006) conducted in Bissau (previously published6) to model the historical changes in smallpox vaccination coverage (see below). The smallpox vaccination scar prevalence is comparable between urban and rural Guinea-Bissau 7 8.…”

Long-term effects of smallpox vaccination on expression of the HIV-1 co-receptor CCR5 in women

“…In addition, studies from Guinea-Bissau and Denmark show that individuals vaccinated against smallpox and/or Bacille-Calmette-Guérin (BCG) had a reduced risk of HIV-1 infection compared with non-vaccinated individuals [ 11 ]. This effect tended to be stronger in women, suggesting a gender-specific effect as seen for other vaccines.…”