دورية أكاديمية
أعرض في EDS

Superior protection in a relapsing Plasmodium cynomolgi rhesus macaque model by a chemoprophylaxis with sporozoite immunization regimen with atovaquone-proguanil followed by primaquine.

التفاصيل البيبلوغرافية
العنوان: Superior protection in a relapsing Plasmodium cynomolgi rhesus macaque model by a chemoprophylaxis with sporozoite immunization regimen with atovaquone-proguanil followed by primaquine.
المؤلفون: Yongvanitchit K; Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand., Kum-Arb U; Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand., Limsalakpetch A; Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand., Im-Erbsin R; Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand., Ubalee R; Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand., Spring MD; Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand., Vesely BA; Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand., Waters N; Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand., Pichyangkul S; Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand. sathitp@afrims.org.
المصدر: Malaria journal [Malar J] 2024 Apr 17; Vol. 23 (1), pp. 106. Date of Electronic Publication: 2024 Apr 17.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101139802 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2875 (Electronic) Linking ISSN: 14752875 NLM ISO Abbreviation: Malar J Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2002-
مواضيع طبية MeSH: Plasmodium cynomolgi* , Malaria Vaccines* , Proguanil* , Atovaquone*, Animals ; Primaquine/therapeutic use ; Sporozoites ; Macaca mulatta ; Immunization ; Chemoprevention ; CD8-Positive T-Lymphocytes ; Drug Combinations
مستخلص: Background: To gain a deeper understanding of protective immunity against relapsing malaria, this study examined sporozoite-specific T cell responses induced by a chemoprophylaxis with sporozoite (CPS) immunization in a relapsing Plasmodium cynomolgi rhesus macaque model.
Methods: The animals received three CPS immunizations with P. cynomolgi sporozoites, administered by mosquito bite, while under two anti-malarial drug regimens. Group 1 (n = 6) received artesunate/chloroquine (AS/CQ) followed by a radical cure with CQ plus primaquine (PQ). Group 2 (n = 6) received atovaquone-proguanil (AP) followed by PQ. After the final immunization, the animals were challenged with intravenous injection of 10 4 P. cynomolgi sporozoites, the dose that induced reliable infection and relapse rate. These animals, along with control animals (n = 6), were monitored for primary infection and subsequent relapses. Immunogenicity blood draws were done after each of the three CPS session, before and after the challenge, with liver, spleen and bone marrow sampling and analysis done after the challenge.
Results: Group 2 animals demonstrated superior protection, with two achieving protection and two experiencing partial protection, while only one animal in group 1 had partial protection. These animals displayed high sporozoite-specific IFN-γ T cell responses in the liver, spleen, and bone marrow after the challenge with one protected animal having the highest frequency of IFN-γ + CD8 + , IFN-γ + CD4 + , and IFN-γ + γδ T cells in the liver. Partially protected animals also demonstrated a relatively high frequency of IFN-γ + CD8 + , IFN-γ + CD4 + , and IFN-γ + γδ T cells in the liver. It is important to highlight that the second animal in group 2, which experienced protection, exhibited deficient sporozoite-specific T cell responses in the liver while displaying average to high T cell responses in the spleen and bone marrow.
Conclusions: This research supports the notion that local liver T cell immunity plays a crucial role in defending against liver-stage infection. Nevertheless, there is an instance where protection occurs independently of T cell responses in the liver, suggesting the involvement of the liver's innate immunity. The relapsing P. cynomolgi rhesus macaque model holds promise for informing the development of vaccines against relapsing P. vivax.
(© 2024. The Author(s).)
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معلومات مُعتمدة: F0517-17 Military Infectious Diseases Research Program (MIDRP)
فهرسة مساهمة: Keywords: Atovaquone-proguanil; Chemoprophylaxis with sporozoite immunization; Relapsing Plasmodium cynomolgi rhesus macaque model; Sporozoite-specific T cell responses
المشرفين على المادة: MVR3634GX1 (Primaquine)
0 (atovaquone, proguanil drug combination)
0 (Malaria Vaccines)
S61K3P7B2V (Proguanil)
0 (Drug Combinations)
Y883P1Z2LT (Atovaquone)
تواريخ الأحداث: Date Created: 20240417 Date Completed: 20240419 Latest Revision: 20240420
رمز التحديث: 20240420
مُعرف محوري في PubMed: PMC11022453
DOI: 10.1186/s12936-024-04933-y
PMID: 38632607
قاعدة البيانات: MEDLINE
الوصف
تدمد:1475-2875
DOI:10.1186/s12936-024-04933-y