NCT01441167

Experimental PfSPZ Vaccine in Adults Without Malaria

Completed Phase 1 Last updated 5 July 2018

What this trial tests

Phase 1 trial testing PfSPZ in Malaria in 64 participants. Completed in 5 June 2013.

Timeline

14 September 2011

Primary endpoint
5 June 2013

5 June 2013

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	64
Start date	14 September 2011
Primary completion	5 June 2013
Estimated completion	5 June 2013
Sites	1 location across United States

Drugs / interventions tested

• PfSPZ — full drug profile →

Conditions studied

• Malaria — all drugs for Malaria →
• Prevention and Control — all drugs for Prevention and Control →
• Acquired Immunity — all drugs for Acquired Immunity →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Adults 18 to 45, any sex, with Malaria or Prevention and Control. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Background:

* Malaria parasites are carried by mosquitoes, which spread the infection by biting people. Currently, there is no effective malaria vaccine. However, studies show that volunteers bitten many times by mosquitoes that carry weakened malaria parasites could fight off getting sick with malaria when later exposed to normal malaria parasites. Malaria parasites are weakened by exposing them to radiation when they are in the stage of development called sporozoites . Only the mosquitoes are irradiated and study volunteers are not exposed to radiation. The radiation stops the parasites from being able to cause disease but still promote protection. For many years, it was not possible to give these sporozoites to people as a vaccine since they could not be adequately purified from the mosquito. Scientists have recently figured out how to produce and isolate the weakened sporozoites so that they can be given in an injected vaccine. This vaccine is known as the "PfSPZ vaccine".
* A malaria challenge will be used to test whether the vaccine will prevent infection. In a malaria challenge, mosquitoes that have the malaria parasite will be allowed to bite a participant's arm. In the event that the vaccine does not work, the malaria parasite used for the challenge can be treated completely with common anti-malaria medications. Participants will be treated immediately if they develop malaria symptoms.

Objectives:

\- To test the safety and effectiveness of the PfSPZ vaccine.

Eligibility:

\- Healthy volunteers between 18 to 45 years of age.

Design:

* Participants will be screened with a physical exam, medical history, and blood tests. There will be five different groups of study participants, all of whom will be monitored with frequent blood tests.
* Group 1 will have two vaccines with the lowest amount of the vaccine given 4 weeks apart, with regular clinic visits up to 24 weeks after the second vaccine. This group will not have a malaria challenge.
* Group 2 will have four or six vaccines given 4 weeks apart at a higher dose than group 1. A malaria challenge will be given about 3 weeks after the last vaccine. Follow-up visits will continue through 24 weeks after the last vaccine.
* Group 3 will have four or six vaccines given 4 weeks apart at a higher dose than group 2. A malaria challenge will be given about 3 weeks after the last vaccination, as for Group 2. Follow-up visits will continue through 24 weeks after last vaccine.
* Group 4 will have four or six vaccines given 4 weeks apart at a higher dose than group 3. A malaria challenge will be given about 3 weeks after the last vaccination. Follow up visits will continue through 24 weeks after last vaccine.
* Group 5 will serve as a control group and will not receive the vaccine, but will have the malaria challenge. Follow-up visits will continue through 8 weeks after the challenge.

All participants from any group who receive a malaria challenge will be treated promptly for malaria when it develops.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Protection against malaria at 1 year and immune correlates following PfSPZ vaccination.
   Ishizuka AS, Lyke KE, DeZure A, Berry AA, et al · · 2016 · cited 299× · PMID 27158907 · DOI 10.1038/nm.4110
2. A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite.
   Kisalu NK, Idris AH, Weidle C, Flores-Garcia Y, et al · · 2018 · cited 250× · PMID 29554083 · DOI 10.1038/nm.4512
3. Sporozoite immunization: innovative translational science to support the fight against malaria.
   Richie TL, Church LWP, Murshedkar T, Billingsley PF, et al · · 2023 · cited 44× · PMID 37571809 · DOI 10.1080/14760584.2023.2245890
4. External quality assurance of malaria nucleic acid testing for clinical trials and eradication surveillance.
   Murphy SC, Hermsen CC, Douglas AD, Edwards NJ, et al · · 2014 · cited 26× · PMID 24838112 · DOI 10.1371/journal.pone.0097398
5. Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein.
   Dacon C, Moskovitz R, Swearingen K, Da Silva Pereira L, et al · · 2025 · cited 14× · PMID 39745947 · DOI 10.1126/science.adr0510
6. Murine infection models for vaccine development: the malaria example.
   Matuschewski K. · · 2013 · cited 11× · PMID 23249712 · DOI 10.4161/hv.23218
7. Increased levels of anti-PfCSP antibodies in post-pubertal females versus males immunized with PfSPZ Vaccine does not translate into increased protective efficacy.
   Kc N, Church LWP, Riyahi P, Chakravarty S, et al · · 2022 · cited 10× · PMID 36389797 · DOI 10.3389/fimmu.2022.1006716
8. Diversify and Conquer: The Vaccine Escapism of <i>Plasmodium falciparum</i>.
   Pance A. · · 2020 · cited 9× · PMID 33171746 · DOI 10.3390/microorganisms8111748