Plasmodium falciparum infection coinciding with the malaria vaccine candidate BK-SE36 administration interferes with the immune responses in Burkinabe children

Abstract

BackgroundA vaccine targeting the erythrocyte stages of Plasmodium falciparum could play a role in preventing clinical disease. BK-SE36 is a promising malaria vaccine candidate that has shown a good safety profile and immunological responses during field evaluations. It was observed that repeated natural infections could result in immune tolerance against SE36 molecule.MethodsThe primary trial was conducted to assess the safety and immunogenicity of the BK-SE36 in two cohorts of children aged 25-60 months (Cohort 1) and 12-24 months (Cohort 2). Immunization was at full dose (1.0 mL) administered at 0, 1, and 6 months. Blood samples were collected before each vaccination for immunological assessments and detection of Plasmodium falciparum infection by microscopy. Blood samples were further collected one month post each vaccination to evaluate immunogenicity.ResultsOf seventy-two (72) subjects that have received BK-SE36 vaccination, 71 had available blood smears during vaccination days. One month post Dose 2, the geometric mean of SE36 antibodies was 263.2 (95% CI: 178.9-387.1) in uninfected individuals compared to 77.1 (95% CI: 47.3-125.7) in infected participants. The same trend was observed one-month post booster dose. Participants uninfected at the time of booster vaccination had significantly higher GMTs compared to those who were infected (424.1 (95% CI: 301.9-595.8) vs. 92.8 (95% CI: 34.9-246.6), p = 0.002. There was a 14.3 (95% CI: 9.7-21.1) and 2.4 (95% CI: 1.3-4.4) fold-change, respectively, in uninfected and infected participants between one-month post Dose 2 and booster. The difference was statistically significant (p < 0.001).ConclusionConcomitant infection by P. falciparum during BK-SE36 vaccine candidate administration is associated with reduced humoral responses. However, it is to be noted that the BK-SE36 primary trial was not designed to investigate the influence of concomitant infection on vaccine-induced immune response and should be interpreted cautiously.Trial registrationWHO ICTRP, PACTR201411000934120.

Persistence of Anti-SE36 Antibodies Induced by the Malaria Vaccine Candidate BK-SE36/CpG in 5–10-Year-Old Burkinabe Children Naturally Exposed to Malaria

“…These can be intrinsic (e.g., sex) and extrinsic (e.g., pre-vaccination titres or infection) [ 22 , 30 , 46 , 47 , 48 , 49 , 50 ]. In a previous BK-SE36 trial (formulation with only aluminium hydroxide gel as adjuvant) in Banfora, Burkina Faso, concurrent P. falciparum infection during vaccination in 12–60-month-old children resulted in lower humoral response compared to the immune response in uninfected children [ 51 ]. Interestingly, in the BK-SE36/CpG arm, the GMT measured in children with (sero-positive) or without (sero-negative) pre-existing titres were similar at D140, D365 and Y3.…”

Malaria prevention in children: an update

“…A blood stage vaccine based on P. falciparum serine repeat antigen 5 is also in testing for the prevention of clinical disease. The vaccine has been shown to be safe and immunogenic, albeit with reduced immunogenicity in the presence of concomitant malaria infection [63,64]. GMZ2, another blood stage vaccine based on glutamaterich protein (GLURP) and merozoite surface protein (MSP) 3 antigens, exhibited no significant vaccine efficacy in 12-35-month-old children and 23% efficacy in 36-60-month-old children [65].…”