Lucy Muthoni Mwai

Background Placental malaria (PM) remains a leading driver of maternal and neonatal mortality, largely attributed to the sequestration of Plasmodium falciparum –infected red blood cells in the placenta. For decades, PM vaccine development has singularly focused on VAR2CSA, the immunodominant variant surface antigen. However, extreme polymorphism, limited cross-strain protection, and the structural complexity of VAR2CSA have hindered the development of a highly efficacious PM vaccine, necessitating a paradigm shift. Methods This review examines existing literature to map potential vaccine antigens implicated in placental malaria ,and outlines a comprehensive vaccine development pipeline. It synthesizes emerging data on antigen expression profiles, immunogenicity, and mechanistic roles in placental pathogenesis. In addition, it highlights both key placental and blood-stage antigens expressed during pregnancy and reviews identification and testing strategies to guide rational PM vaccine design. Results This Review maps the expanding antigenic landscape of PM beyond VAR2CSA, identifying non-canonical surface and exported proteins, including SURFINs, PHISTs, PfRON3, and Pf CSA-L, as critical targets that may circumvent current bottlenecks. The findings highlight the relevance of these antigens in placental malaria pathogenesis and their potential as alternative or complementary vaccine candidates. Conclusions Furthermore, we propose an integrated framework for rational vaccine design that couples high-throughput antigen discovery and structural immunogen engineering with multivalent formulation strategies. By bridging the gap between molecular parasitology and translational immunology, this roadmap offers a strategic path toward a broadly protective placental malaria (PM) vaccine.

In pregnancy, fetal health, growth and development are dependent on normal placental development. However, the mechanisms that support maternal immune tolerance for the fetus, fetal nourishment, and pregnancy maintenance to term are not fully understood. Placental secretions into the intervillous space play a key role in shaping early placental function. In their entirety, they represent the pregnancy-associated secretome (PAS). PAS alterations have been associated with various complications such as fetal growth restriction, maternal anemia, and preterm birth. Placental malaria (PM), caused by the sequestration of Plasmodium falciparum-infected erythrocytes in the intervillous space, affects PAS composition. In this review, we explore how P. falciparum-induced changes of PAS may contribute to pathogenesis and immune dysregulation during pregnancy, as well as the possibilities of leveraging PAS components as biomarkers for the prevention, diagnosis, and management of PM.

Cervical cancer caused mainly by high risk human papillomavirus (HPV) 16 and 18 strains is the second most prevalent cancer of women in Kenya. It is often diagnosed late when treatment is difficult due to very low percentage of women attending screening thus, mortalities remain high. The most available tests in low-and-middle-income countries (LMICs) have relatively low specificity, low sensitivity, require a laboratory setting and huge technical and financial support not readily available. HPV 16/18 E6 oncoprotein has been identified as a potential biomarker in a more specific early diagnosis of cervical cancer. This retrospective cross-sectional study developed a paper-based nanokit with enhanced detection of HPV 16/18 E6 oncoprotein for cervical cancer screening. The HRP labelled antibodies HPV 16 E6/18 E6-HRP (CP15) passively conjugated to citrate stabilized 20nm gold nanoparticles were evaluated for immune sensing mechanism using a recombinant viral HPV E6 protein. The diagnostic accuracy was evaluated using 50 tissue lysates from formalin fixed paraffin embedded cervical biopsy, including control (n=10), Mild Dysplasia (n=10), Cervical intraepithelial neoplasia 3 (CIN3) (n=10), Cervical intraepithelial neoplasia 4 (CIN4) (n=10) and invasive carcinoma (n=10). The molecular technique used was dot blot molecular assay. A positive result was generated by catalytic oxidation of peroxidase enzyme on 3,3’,5,5’-Tetramethylbenzidine (TMB) substrate. The gold nanoparticles were used to enhance the signal produced by peroxidase activity of horseradish peroxidase (HRP) enzyme giving a more sensitive assay as compared to use of non-conjugated antibody. This study provides a significantly high and reliable diagnostic accuracy for precancerous and cancerous lesions with a sensitivity of 90%, a specificity of 90%, a likelihood ratio for positive and negative tests as 9:1 and 1:9 respectively, a Positive Predictive Value of 97.3% and a Negative Predictive Value of 69.2%. This study avails a sensitive, rapid test using paper-based nanotechnology which can be utilised in community-based screening outreaches particularly in low- and middle-income countries.

Gold nanoparticle (AuNP) bioconjugates are increasingly being utilised in biomedicine due to their low toxicity on biological tissues and unique electronic and chemical properties. They have been utilised in several biological applications namely manufacture of nanomaterials, biosensing, electron microscopy and drug delivery systems. Particularly, immuno-assays often employ gold nanoparticles (AuNPs) to enhance detection of a biological component. This paper presents a study on the bioconjugation of AuNPs with Horse Radish Peroxidase conjugated Human Papilloma Virus 16/18 Early 6 antibodies (CIP5) against Early 6 (E6) oncoprotein that is overexpressed in cervical carcinoma progression through physical adsorption. This bioconjugate can be employed in diagnostic immunoassay for cervical cancer screening. The study also demonstrated that the antibody pI, gold colloidal solution pH and amount of antibody determine the generation of stable Antibody–AuNPs bioconjugates.