Effect of malaria parasitaemia on antibody responses to single-dose and two-dose HPV vaccination: results from the DoRIS dose-reduction immunogenicity trial in Tanzanian girls

BACKGROUND: Human papillomavirus (HPV) vaccination is a key component of the World Health Organization's global strategy for cervical cancer elimination. The effect of malaria, a known immunomodulator, on HPV vaccine immunogenicity is poorly understood. This study assessed the effect of malaria parasitaemia at the time of vaccination on HPV vaccine immune responses among participants in a dose-reduction immunogenicity trial (DoRIS). METHODS AND FINDINGS: 930 HIV-negative Tanzanian schoolgirls aged 9-14 years were randomised to receive one, two or three doses of Cervarix® or Gardasil®9 (155 per arm) and followed to month (M)36. One-dose and two-dose arms participants were enrolled in a long-term extension and are included in this malaria sub-study. Dried blood spots at each vaccination visit were tested for malaria parasitaemia by quantitative polymerase chain reaction. HPV16/18 antibody responses were measured at M12, 24, 36 and 60. In the one-dose arms, there was no evidence of a difference in antibody geometric mean concentrations (GMC) or avidity index (AI) between participants with and without malaria at the time of vaccination. In the two-dose Cervarix® arm, M36 HPV16 antibody GMCs and AI results were lower in participants with malaria at either vaccination visit (HPV16 GMC ratio = 0.74, 95%CI = 0.55-0.99; AI ratio = 0.95, 95%CI = 0.91-0.99). In the two-dose Gardasil®9 arm, M36 HPV18 antibody GMCs and AI results were lower in participants with malaria at the first vaccine dose than those without malaria (HPV18 GMC ratio = 0.58, 95%CI = 0.37-0.92; AI ratio = 0.93, 95%CI = 0.87-0.99). These trends were also observed at M60. CONCLUSIONS: Whilst some effect of malaria on antibody responses was observed in the two-dose arms, these were mostly small in magnitude and unlikely to have clinical significance. Single-dose arms results are reassuring but further evaluations in larger populations would be valuable to confirm the findings. The potential for an effect of moderate or severe infection with greater parasite burden remains unclear. (NCT02834637).