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Background <p>Few well-established in vivo animal models reflect the complexity of human malaria infection and immunity, and even fewer have been predictive of the potential of malaria vaccines or prophylactic therapies. Here, we characterized and optimized an <i>Aotus nancymaae</i> non-human primate (NHP) model of <i>Plasmodium vivax</i> (Pv) blood stage infection to enable the testing of novel vaccines and immunoprophylactics.</p> Methods <p>Using direct blood stage infection, we selected Vietnam-IV as the most virulent <i>P. vivax</i> strain from seven monkey adapted strains. We next determined the infectious dose with the lowest variability at doses of 0.3 (n = 3), 1.0 (n = 6) and 2.5 (n = 3) × 10^6 infected red blood cells (iRBC) in spleen-intact <i>A. nancymaae</i> non-human primates (NHPs). In addition, complete blood count (CBC) was measured during blood stage infection. Genomic sequencing was performed for <i>P. vivax</i> Vietnam-IV candidate Duffy Binding Protein-II. Finally, we evaluated the efficacy of a monoclonal antibody (mAb 099100) against DBP-II to protect against blood infection challenge.</p> Results <p>The <i>P. vivax</i> Vietnam-IV monkey adapted strain at dose of 2.5 × 10^6 gave infection kinetics with the lowest coefficient variation (15–23%). CBC results at a low (0.3 × 10^6) and high (2.5 × 10^6) dose showed a significant increase in lymphocytes (5.0–5.3 to 7.0–8.5 10^9/l) and a decrease of neutrophils (1.9–3.0 to 0.6–1.2) and platelets (413–458 to 23–68 10^9/l) during acute infection. In a pilot study testing the anti-DBPII mAb 099100, we observed that 1 of 3 monkeys was partially protected against <i>P. vivax</i> as measured by need for treatment intervention (compared with 0 out of 3 monkeys in the control group). <i>P. vivax</i> Vietnam-IV genomic data showed that line was a single clone with a single gene copy of blood stage <i>PvDBPII</i> with single nucleotide polymorphisms outside mAb binding sites.</p> Conclusions <p>Our study showed a <i>P. vivax</i> blood stage <i>A. nancymaae</i> model with well-characterized clinical, hematological and serological parameters during the course of infection. The challenge appeared stringent and suggests a high titer or high potency of mAb is needed for protection. This model can set the foundation for the evaluation of emerging <i>P. vivax</i> blood stage vaccines, monoclonal antibodies, anti-malarial drugs and prophylactics.</p>

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Development of novel Aotus nancymaae non-human primate model for the evaluation of Plasmodium vivax blood stage vaccines and immunoprophylactics

  • 期刊论文

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  • 发表日期：

    2026年6月3日

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  • Julio A. Ventocilla,
  • L. Lorena Tapia,
  • Fredy E. Villena,
  • Diana Cedamanos,
  • Jessica Buchta,
  • Danielle Pannebaker,
  • Hugo O. Valdivia,
  • Karli R. Redinger,
  • Jürgen Bosch,
  • Lenore Carias,
  • Berlin Londono-Renteria,
  • Christopher King,
  • Brandon K. Wilder

摘要

Background

Few well-established in vivo animal models reflect the complexity of human malaria infection and immunity, and even fewer have been predictive of the potential of malaria vaccines or prophylactic therapies. Here, we characterized and optimized an Aotus nancymaae non-human primate (NHP) model of Plasmodium vivax (Pv) blood stage infection to enable the testing of novel vaccines and immunoprophylactics.

Methods

Using direct blood stage infection, we selected Vietnam-IV as the most virulent P. vivax strain from seven monkey adapted strains. We next determined the infectious dose with the lowest variability at doses of 0.3 (n = 3), 1.0 (n = 6) and 2.5 (n = 3) × 10^6 infected red blood cells (iRBC) in spleen-intact A. nancymaae non-human primates (NHPs). In addition, complete blood count (CBC) was measured during blood stage infection. Genomic sequencing was performed for P. vivax Vietnam-IV candidate Duffy Binding Protein-II. Finally, we evaluated the efficacy of a monoclonal antibody (mAb 099100) against DBP-II to protect against blood infection challenge.

Results

The P. vivax Vietnam-IV monkey adapted strain at dose of 2.5 × 10^6 gave infection kinetics with the lowest coefficient variation (15–23%). CBC results at a low (0.3 × 10^6) and high (2.5 × 10^6) dose showed a significant increase in lymphocytes (5.0–5.3 to 7.0–8.5 10^9/l) and a decrease of neutrophils (1.9–3.0 to 0.6–1.2) and platelets (413–458 to 23–68 10^9/l) during acute infection. In a pilot study testing the anti-DBPII mAb 099100, we observed that 1 of 3 monkeys was partially protected against P. vivax as measured by need for treatment intervention (compared with 0 out of 3 monkeys in the control group). P. vivax Vietnam-IV genomic data showed that line was a single clone with a single gene copy of blood stage PvDBPII with single nucleotide polymorphisms outside mAb binding sites.

Conclusions

Our study showed a P. vivax blood stage A. nancymaae model with well-characterized clinical, hematological and serological parameters during the course of infection. The challenge appeared stringent and suggests a high titer or high potency of mAb is needed for protection. This model can set the foundation for the evaluation of emerging P. vivax blood stage vaccines, monoclonal antibodies, anti-malarial drugs and prophylactics.