Comparative intravital imaging of human and rodent malaria sporozoites reveals the skin is not a species‐specific barrier

• Published in: EMBO molecular medicine Vol. 13; no. 4; pp. e11796 - n/a
• Main Authors: Hopp, Christine S, Kanatani, Sachie, Archer, Nathan K, Miller, Robert J, Liu, Haiyun, Chiou, Kevin K, Miller, Lloyd S, Sinnis, Photini
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09-04-2021; John Wiley & Sons, Inc; EMBO Press; John Wiley and Sons Inc; Springer Nature
• Subjects: Animal models; Antibodies; Automation; Blood vessels; Clinical trials; EMBO22; EMBO23; Erythrocytes; Health aspects; Immunization; Infection; Infections; intravital; Liver; Malaria; Microscopy; Mosquitoes; Motility; Parasites; Plasmodium; Plasmodium falciparum; Proteins; Skin; Software; Species; Sporozoites; Vaccines; Viral antibodies; Xenografts; Fiji; skin; intravital; malaria; sporozoites; Plasmodium
• ISSN: 1757-4676; 1757-4684
• DOI: 10.15252/emmm.201911796

Malaria infection starts with the injection of
Plasmodium
sporozoites into the host’s skin. Sporozoites are motile and move in the skin to find and enter blood vessels to be carried to the liver. Here, we present the first characterization of
P. falciparum
sporozoites
in vivo
, analyzing their motility in mouse skin and human skin xenografts and comparing their motility to two rodent malaria species. These data suggest that in contrast to the liver and blood stages, the skin is not a species‐specific barrier for
Plasmodium
. Indeed,
P. falciparum
sporozoites enter blood vessels in mouse skin at similar rates to the rodent malaria parasites. Furthermore, we demonstrate that antibodies targeting sporozoites significantly impact the motility of
P. falciparum
sporozoites in mouse skin. Though the sporozoite stage is a validated vaccine target, vaccine trials have been hampered by the lack of good animal models for human malaria parasites. Pre‐clinical screening of next‐generation vaccines would be significantly aided by the
in vivo
platform we describe here, expediting down‐selection of candidates prior to human vaccine trials.
Synopsis
We show that human and rodent malaria sporozoites move and enter blood vessels with similar efficiency in mouse skin. Our data demonstrate that intravital imaging of
P. falciparum
sporozoites at the dermal inoculation site can be used to assess the impact of antibody on sporozoite migration.
Rodent and human malaria sporozoites move in mouse skin with similar speeds and displacements, and enter blood vessels with equal efficiency, indicating that this is not a species‐specific barrier to infection.
In human skin xenografts, a greater proportion of
P. falciparum
sporozoites are motile, suggesting some species‐specific signals may exist.
Intravital imaging of
P. falciparum
sporozoites in the skin of passively immunized mice, is a platform that can be utilized to test the inhibitory activity of antibody on human malaria sporozoites in vivo.
Graphical Abstract
We show that human and rodent malaria sporozoites move and enter blood vessels with similar efficiency in mouse skin. Our data demonstrate that intravital imaging of
P. falciparum
sporozoites at the dermal inoculation site can be used to assess the impact of antibody on sporozoite migration.