Plasmodium sporozoites trickle out of the injection site

Abstract

In the Introduction to our article, we supported a statement about the loss of infectivity of sporozoites following in vitro incubation with an inappropriate citation: Vanderberg, J.P. (1975)

A long and winding road: The Plasmodium sporozoite's journey in the mammalian host

“…Using a PCR approach we had remarkably concordant results with the finding that 20% of the inoculum was associated with the draining lymph node 3 hrs after intradermal inoculation of sporozoites [20]. Together these findings suggest that in natural infection, the draining lymph node may be the site at which the immune response to the sporozoite stage is initiated and indeed it has been recently demonstrated that a sporozoite-specific cytotoxic T-cell (CTL) response is evident in the draining lymph node just 2 days after intradermal immunization with irradiated sporozoites [Chakravaraty and Zavala, unpublished data].…”

“…Although this had never been formally demonstrated, the waning infectivity of sporozoites dissected from mosquito salivary glands and kept at 37°C for 1 hr [19] combined with the fact that some sporozoites do enter the blood circulation within minutes of injection [12], led to the belief that if sporozoites had not left the injection site soon after their injection, they likely never would. Using a quantitative PCR approach to measure the kinetics with which the majority of sporozoites left the injection site, we found that when injected intradermally, either by needle or mosquito bite, about 90% of sporozoites remain at the injection site 1 hr post injection [20]. Indeed, if the injection site was removed 1 hr after sporozoite inoculation, parasite burden in the liver was reduced by 90 to 95%.…”

“…Subinoculation experiments showed that the blood of mice inoculated intradermally with sporozoites was infectious, albeit with low numbers of sporozoites, to naïve mice for hours. Thus, sporozoites remain viable and infective for a prolonged period of time in the mammalian host and leave the injection site in a slow trickle [20].…”

Efficacy model for antibody-mediated pre-erythrocytic malaria vaccines

“…The mechanics of sporozoite inoculation may further define vaccine type. When sporozoites are injected into the skin, they remain at the bite site for up to an hour [8,9]. Anti-sporozoite antibodies may opsonize and remove those remaining in the skin but fail to protect against those that enter the bloodstream quickly.…”

“…However, every bite can inject from 0 to 100þ sporozoites [6,7], with the probability of blood-stage infection increasing for larger doses. Sporozoites that have been deposited in the skin or capillaries will remain at the injection site for up to an hour before trickling into the blood stream and migrating to the liver [8,9]. Sporozoites are susceptible to antibody opsonization from immunoglobulin G (IgG) antibodies, recognizing sporozoite antigens at any stage in this journey [10].…”