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. 2023 Aug 31;41(38):5494-5498.
doi: 10.1016/j.vaccine.2023.07.067. Epub 2023 Aug 8.

Preliminary studies on the immunogenicity of a prime-and-trap malaria vaccine in nonhuman primates

Melanie J Shears  1 , Felicia N Watson  2 , Brad C Stone  2 , Irene Cruz Talavera  2 , Chaitra Parthiban  2 , Jokichi Matsubara  2 , Natasha Kc  3 , B Kim Lee Sim  3 , Stephen L Hoffman  3 , Sean C Murphy  4
Affiliations

Preliminary studies on the immunogenicity of a prime-and-trap malaria vaccine in nonhuman primates

Melanie J Shears et al. Vaccine. .

Abstract

Development of next-generation vaccines against Plasmodium falciparum (Pf) is a priority. Many malaria vaccines target the pre-erythrocytic sporozoite (SPZ) and liver stages. These include subunit vaccines based on the Pf circumsporozoite protein (CSP) and attenuated PfSPZ vaccines. However, these strategies require 3-4 doses and have not achieved optimal efficacy against field-transmitted malaria. Prime-and-trap is a recently developed two-step heterologous vaccine strategy that combines priming with DNA encoding CSP followed by a single dose of attenuated SPZ. This strategy aims to induce CD8+ T cells that can eliminate parasites in the liver. Prior data has demonstrated that prime-and-trap with P. yoelii CSP and PySPZ was immunogenic and protective in mice. Here we report preliminary data on the immunogenicity of PfCSP prime and PfSPZ trap vaccine in rhesus macaques. This vaccine induced PfCSP-specific antibodies and T cell responses in all animals. However, response magnitude differed between individuals, suggesting further study is required.

Keywords: Macaque; Malaria; Vaccine.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S. C. M. filed a patent application on selected aspects of the prime-and-trap concept through the University of Washington. S. C. M. has equity in a startup company (Sound Vaccines, Inc.) that is negotiating with the University of Washington for rights to this intellectual property. The relationship between the authors and Sound Vaccines, Inc., has been reviewed by the University of Washington and complies with all University and State of Washington policies on such activities. N.K.C., B. K. L. S., and S. L. H. are paid employees of Sanaria Inc.

Figures

Figure 1.
Figure 1.. Study diagram.
Groups of n=3 rhesus macaques were vaccinated as follows. Group 1 received mock vaccines consisting of DNA encoding no antigen delivered by gene gun on day 0 (grey circle) and vaccine diluent only administered intravenously on days 0, 7 and 28 (grey triangle). Group 2 received the prime-and-trap vaccine consisting of 15 ug DNA encoding the near full-length PfCSP and LT adjuvant administered by gene gun on day 0 (gold circle), followed by 3x106 attenuated PfSPZ administered intravenously on day 28 (red triangle). Group 3 received a comparator vaccine consisting of three doses of 1x106 attenuated PfSPZ administered intravenously on days 0, 7 and 28 (red triangle). All groups had a liver biopsy on day 56. All groups received 1x106 non-attenuated PfSPZ administered intravenously on day 84 or 85 as a recall exposure (black triangle). Necropsies for all animals occurred on day 90 or 91.
Figure 2.
Figure 2.. Cellular response to vaccination as measured by PfCSP peptide IFNγ ELISPOT. Inset: Table of animal characteristics.
A. Responses in liver lymphocytes obtained post-vaccination by surgery on day 56. B. Responses in liver lymphocytes from six days post-PfSPZ recall exposure at necropsy. C. Responses in PBMCs on days 0, 56, and 84. D. Responses in splenocytes from six days post-PfSPZ recall exposure at necropsy. Animal ID and vaccine treatment group given below x-axis. nSFU, normalized spot forming units. Animals were considered to have responded if nSFU per million cells was ≥10 fold greater than baseline for PBMCs or ≥10 fold greater than mock vaccinated controls for liver lymphocytes and splenocytes.
Figure 3.
Figure 3.. Humoral response to vaccination as measured by PfCSP ELISA.
Plasma was collected at baseline, on day 28 before final vaccination, and post-vaccination on day 56 and 84. The net OD 1.0 was calculated by subtracting the baseline OD 1.0 from the sample OD 1.0. Data for individual animals is shown as circles. Error bars show mean and range for each vaccine treatment group.
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