The evaluation of anti-envelope antibodies in patient plasmas infected with human immunodeficiency virus type 1 subtype CRF01_AE

• Main Author: Ng, Qi Ron
• Format: Thesis
• Published: 2020
• Subjects: QR Microbiology; QR180 Immunology
• Online Access: http://eprints.sunway.edu.my/2430/

Over three decades has passed since human immunodeficiency virus type 1 (HIV-1) was identified as the causative agent of acquired immunodeficiency syndrome (AIDS), but a clinical vaccine has yet to be available to the public. The envelope glycoprotein (Env) on the surface of HIV-1 is the antigenic target of the immune system where antibodies are elicited against and is also the focus in its vaccine design. In chronic HIV-1 patients, there is a chance of the development of broadly neutralizing antibodies (bnAbs) with cross-subtype neutralizing efficacies against HIV-1. Isolating these bnAbs from infected patient serums have greatly assisted in identifying the sites of vulnerability on Env. A goal since the discoveries of these bnAbs is to design a vaccine immunogen that could stimulate the production of these potent antibodies for protective immunity, but this has proved to be a challenge. Among the many subtypes of HIV-1, CRF01_AE is the focus of this research project as it is the prevalent HIV-1 subtype infecting the Malaysian population. HIV-1 is extremely antigenically variable and it stands to be more reasonable to design a vaccine immunogen targeting a specific subtype for a specific geographical region. Studying and understanding the Env of this subtype is also important for the benefit of infected Malaysians because there is a lack of data on the type/class of antibody elicited in a CRF01_AE-infected Malaysian. The overarching aim of this project is to investigate the prevalence and potencies of anti-Env neutralizing antibodies (nAbs) elicited among a pool of donors infected with HIV-1 subtype CRF01_AE. ELISA and neutralization assays were conducted to analyse the neutralizing response in a pool of plasma donors infected with CRF01_AE against multiple subtype HIV-1 recombinant proteins and pseudovirions. HIV-1 mutant pseudovirions were also used to investigate potential amino acids on the HIV-1 glycoprotein that regulates neutralizing capacity of the infected plasmas. 14% of plasmas (3 out of 21) showed nAb response with considerable breadth. One of them, P9, demonstrates trimeric Env specificity and consists of nAbs targeting the Env V1/V2 and CD4bs region. Furthermore, the N187 and N354 glycans were found to not be the determinants for two plasmas’, P133 and P138, type-specific potency against two CRF01_AE strains C1080 and CM246. Overall, this pilot study demonstrates that CRF01_AE-infected individuals from Malaysia could elicit nAbs with considerable breadth and could lead to the foundation for HIV-1 vaccine development for the Malaysian population.