Adukpo, S. | bioRxiv Science

bioRxiv2026

Promising antimicrobial activity of Moringa oleifera seed extract fractions

This study investigated the antiplasmodial and antibacterial activities of fractionated extracts of Moringa oleifera seeds, focusing on the influence of solvent polarity on bioactivity. The results revealed a polarity-dependent distribution of activity. Polar aqueous extracts (crude and residual fractions) exhibited the most pronounced antiplasmodial effects against Plasmodium falciparum (3D7 strain), with IC values of 107-135 {micro}g/mL. Time-dependent analyses of the crude and residual fractions showed that parasitaemia declined steadily over time, and consequently, percentage inhibition increased with time, with both extracts reaching 70-80% inhibition by 48 hours at higher concentrations. In contrast, moderately polar organic fractions, notably ethyl acetate and dichloromethane, demonstrated strong antibacterial activity against both Gram-positive and Gram-negative clinical isolates, including resistant strains such as MRSA and ESBL-producing Escherichia coli. Minimum inhibitory concentrations (MICs) ranged from 6.3 to 25 mg/mL for the ethyl acetate fraction, and all active fractions exhibited bactericidal properties (MBC/MIC [≤] 4). Comparative analysis showed that while antiplasmodial activity was moderate relative to the standard drug (chloroquine), antibacterial activity was robust and clinically promising. Fractionation revealed that distinct phytochemical classes underlie the two activities: polar compounds appear responsible for antiplasmodial effects, whereas moderately polar compounds drive antibacterial potency. The moderate antiplasmodial activity is significant in the context of adjunctive therapy and resistance management, while the strong antibacterial activity is highly relevant to the global challenge of antimicrobial resistance. Together, the results position Moringa oleifera as a promising source of phytochemicals for integrated infectious disease management, particularly in regions where malaria and bacterial co-infections are prevalent.

microbiology↗

bioRxiv2020

Mapping of safe and early chemo-attenuated live Plasmodium falciparum immunization identifies immune signature of vaccine efficacy

Potent protection against malaria can be induced by attenuated live-immunization with Plasmodium falciparum (Pf) sporozoites (SPZ). However, a better understanding of the critical processes involved in the establishment of protective immunity is needed. We explored the safety and vaccine efficacy of early chemo-attenuation of PfSPZ under atovaquone-proguanil (AP). AP caused early arrest of P. berghei liver stages. Despite the absence of replication, robust protection in mice correlated with parasite-specific effector-memory CD8+ T-cell responses. In a phase I clinical trial a single dose of AP prevented Pf infections in the liver of adult, human subjects who received three doses of 5.12x104 or 1.5x105 PfSPZ by direct venous inoculation combined with oral AP. However, only 2 of 8 (25%) and 2 of 10 (20%), respectively, were protected against controlled human malaria infection (CHMI) 10 weeks after the last vaccine dose, despite levels of IgG antibodies to the Pf circumsporozoite protein (PfCSP) comparable to those achieved in fully protected volunteers after immunization with 5.12x104 PfSPZ with chloroquine chemoprophylaxis active only against subsequent blood stages. We identify lower IgG recognition of the secreted liver stage-specific antigens LISP2 and LSA1 and the multi-stage antigen MSP5 as immune signatures of inferior vaccine efficacy compared to PfSPZ with chloroquine chemoprophylaxis. In conclusion, we show that immune signatures of liver stage antigens, but neither an established rodent malaria model nor concentrations of antibodies against the major surface protein of sporozoites, permit prediction of vaccine efficacy. Thus, this study provides a clear rationale for the development of live sporozoite vaccination protocols that boost exposure to Pf liver stage antigens. Significance StatementOur research demonstrates that attenuation of liver infection of high doses of Plasmodium falciparum sporozoites by concomitant single-dose administration of atovaquone-proguanil is safe in humans. However, vaccine efficacy was modest when compared to an identical protocol using chloroquine that acts only on the subsequent blood infection. Immune signatures of secreted P. falciparum liver stage antigens, but neither an established rodent malaria model nor concentrations of sporozoite antibodies, permit prediction of vaccine efficacy.

immunology↗