Chronic Immune Activation and CD4+ T Cell Lymphopenia in Healthy African Individuals: Perspectives for SARS-CoV-2 Vaccine Efficacy

Abstract

Chronic immune activation has been considered as the driving force for CD4⁺ T cell depletion in people infected with HIV-1. Interestingly, the normal immune profile of adult HIV-negative individuals living in Africa also exhibit chronic immune activation, reminiscent of that observed in HIV-1 infected individuals. It is characterized by increased levels of soluble immune activation markers, such as the cytokines interleukin (IL)-4, IL-10, TNF-α, and cellular activation markers including HLA-DR, CD-38, CCR5, coupled with reduced naïve and increased memory cells in CD4⁺ and CD8⁺ subsets. In addition, it is accompanied by low CD4⁺ T cell counts when compared to Europeans. There is also evidence that mononuclear cells from African infants secrete less innate cytokines than South and North Americans and Europeans in vitro. Chronic immune activation in Africans is linked to environmental factors such as parasitic infections and could be responsible for previously observed immune hypo-responsiveness to infections and vaccines. It is unclear whether the immunogenicity and effectiveness of anti-SARS-CoV-2 vaccines will also be reduced by similar mechanisms. A review of studies investigating this phenomenon is urgently required as they should inform the design and delivery for vaccines to be used in African populations.

Keywords: Africa; COVID-19; SARS-CoV-2; chronic immune activation; helminths; hyporesponsiveness; vaccine.

Figure 1

Chronic immune activation in apparently health Africans may be related to leaky gut, co-infections (such as helminths, CMV, HCV and latent TB infection) results in activation-induced CD4⁺ T cell apoptosis. In turn, depletion of CD4⁺ T cells may result in decreased response to SARS-CoV-2 vaccine in the African population. CMV, cytomegalovirus; HCV, hepatitis C virus; TB, tuberculosis.