{"title":"A novel prophylactic strategy to enhance immunity in Plasmodium berghei infected mice: Combining mefloquine and ultra-diluted malarial antigen","authors":"Mansi Suri , Sapna Katnoria , Jyoti Joshi , Subhash Kaushik , Debadatta Nayak , Sukhbir Kaur","doi":"10.1016/j.micpath.2025.107890","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Antimalarial drug resistance poses a significant challenge towards global efforts to combat malaria, so new strategies must be explored. Previously we showed promising antimalarial activity of ultra diluted malarial antigen (UdMAg), a novel biotherapic drug which was developed from <em>in vitro</em> cultures of a combination of cell-free parasites and infected red blood cells from <em>Plasmodium falciparum</em> 3D7 (chloroquine sensitive) and RKL-9 strains (chloroquine resistant). The stock was collected and sent to Dr. Willmar Schwabe India Pvt. Ltd., New Delhi for preparing its homeopathic dilutions to 30c by repeated succussions and potentization. The final ultradiluted Malarial antigen 30c (UdMAg) was used for the treatment along with the standard antimalarial drug mefloquine (MQ) not only to enhance the therapeutic outcomes but also ameliorate its side effects.</div></div><div><h3>Methods</h3><div>The prophylactic efficacy of MQ in combination with UdMAg was assessed in <em>P. berghei</em> infected mice (ANKA strain) using Peters (1980) method. Assessment of parasitaemia and mean survival time was studied along with immunological parameters which included analysis of cell surface expression, nitric oxide (NO) concentration, and reactive oxygen species (ROS) levels.</div></div><div><h3>Results</h3><div>The results demonstrated enhanced prophylactic efficacy of the MQ, accompanied by 100 % mean survival time when given along with UdMAg. Further, the combination treatment exhibited improved immunological responses, increased concentration of nitric oxide and reactive oxygen specie levels.</div></div><div><h3>Discussion & conclusion</h3><div>MQ, a standard antimalarial has significant side-effects, so a novel antimalarial (UdMAg) was used as a biotherapy in combination to improve its prophylactic efficacy through the generation of immune responses in the host. Our findings highlight the potential of UdMAg in enhancing the prophylactic efficacy of standard antimalarial drug.</div><div>This novel integrative approach strengthens the impact of standard antimalarial treatment while offering a potential avenue for immune-based prophylaxis. Such an approach may have significant translational relevance for developing adjunct therapies in malaria-endemic regions, particularly where immune resilience is crucial.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"207 ","pages":"Article 107890"},"PeriodicalIF":3.5000,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microbial pathogenesis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0882401025006151","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction
Antimalarial drug resistance poses a significant challenge towards global efforts to combat malaria, so new strategies must be explored. Previously we showed promising antimalarial activity of ultra diluted malarial antigen (UdMAg), a novel biotherapic drug which was developed from in vitro cultures of a combination of cell-free parasites and infected red blood cells from Plasmodium falciparum 3D7 (chloroquine sensitive) and RKL-9 strains (chloroquine resistant). The stock was collected and sent to Dr. Willmar Schwabe India Pvt. Ltd., New Delhi for preparing its homeopathic dilutions to 30c by repeated succussions and potentization. The final ultradiluted Malarial antigen 30c (UdMAg) was used for the treatment along with the standard antimalarial drug mefloquine (MQ) not only to enhance the therapeutic outcomes but also ameliorate its side effects.
Methods
The prophylactic efficacy of MQ in combination with UdMAg was assessed in P. berghei infected mice (ANKA strain) using Peters (1980) method. Assessment of parasitaemia and mean survival time was studied along with immunological parameters which included analysis of cell surface expression, nitric oxide (NO) concentration, and reactive oxygen species (ROS) levels.
Results
The results demonstrated enhanced prophylactic efficacy of the MQ, accompanied by 100 % mean survival time when given along with UdMAg. Further, the combination treatment exhibited improved immunological responses, increased concentration of nitric oxide and reactive oxygen specie levels.
Discussion & conclusion
MQ, a standard antimalarial has significant side-effects, so a novel antimalarial (UdMAg) was used as a biotherapy in combination to improve its prophylactic efficacy through the generation of immune responses in the host. Our findings highlight the potential of UdMAg in enhancing the prophylactic efficacy of standard antimalarial drug.
This novel integrative approach strengthens the impact of standard antimalarial treatment while offering a potential avenue for immune-based prophylaxis. Such an approach may have significant translational relevance for developing adjunct therapies in malaria-endemic regions, particularly where immune resilience is crucial.
期刊介绍:
Microbial Pathogenesis publishes original contributions and reviews about the molecular and cellular mechanisms of infectious diseases. It covers microbiology, host-pathogen interaction and immunology related to infectious agents, including bacteria, fungi, viruses and protozoa. It also accepts papers in the field of clinical microbiology, with the exception of case reports.
Research Areas Include:
-Pathogenesis
-Virulence factors
-Host susceptibility or resistance
-Immune mechanisms
-Identification, cloning and sequencing of relevant genes
-Genetic studies
-Viruses, prokaryotic organisms and protozoa
-Microbiota
-Systems biology related to infectious diseases
-Targets for vaccine design (pre-clinical studies)