Date of Award

3-10-2026

Thesis Type

Masters

Document Type

Dissertation

Divisions

Institute for Advanced Studies

Institution

Universiti Malaya

Abstract

The simultaneous circulation of COVID-19 and influenza A presents a major public health challenge in Malaysia, where both viruses are widespread and continue to cause significant morbidity and mortality. Despite the successful rollout of COVID-19 vaccination programs and the development of natural immunity among recovered individuals, the potential interactions between SARS-CoV-2 antibodies and other prevalent respiratory diseases, such as influenza A, remain poorly understood. This research was undertaken to address this critical gap, focusing on two key immunological phenomena which are cross-reactive immunity, where antibodies generated by one infection may neutralize another virus, and antibody-dependent enhancement (ADE), where antibodies may inadvertently facilitate viral entry and worsen infection outcomes. This study has the following objectives: (1) to examine the cross-neutralization of SARS-CoV-2 antibodies against subsequent influenza A virus infection, (2) to assess the potential for ADE by SARS-CoV-2 antibodies during subsequent influenza A virus infection, and (3) to examine the cytokine profile alterations in ADE culture supernatants following influenza A virus infection in the presence of SARS-CoV-2 antibodies. To achieve these aims, the study utilized archived serum samples collected from both pre-COVID-19 and post-COVID-19 eras. Samples were screened for the presence of anti-influenza A IgG and subsequently grouped into four distinct groups based on their serological status. Neutralizing antibody titers against influenza A virus were determined by inoculating serum-virus mixtures onto MDCK cells, with H1N1 RNA quantified using real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR). The potential for ADE was assessed using U937 cells, which express Fc receptors, to determine whether SARS-CoV-2 antibodies could enhance influenza A virus infection. Additionally, the study evaluated changes in immune profiles by measuring concentrations of key cytokines and chemokines including MCP-1, IL-10, RANTES, IL-1Ra, and IFN-β by using commercial ELISA kits. For cross-neutralization assay, the test group (anti-SARS-CoV-2 IgG-positive) showed non-significant viral load reductions of 28% at 1:320 dilution and 37% at 1:1280 dilution when compared to the double negative group, indicating that prior infection with or vaccination against COVID-19 does not confer substantial protection against influenza A. However, a subset of samples demonstrated mild enhancement of influenza A virus infection in the ADE assay, with a modest ~4-fold increase in mean viral RNA values observed when comparing the double negative group to the anti-SARS-CoV-2 IgG-positive group at the 1:100 dilution, suggesting the possibility of a limited risk of ADE in individuals with prior SARS-CoV-2 exposure. Furthermore, cytokine and chemokine profiling indicated elevated levels of pro-inflammatory markers, notably MCP-1 and RANTES, and suppression of anti-inflammatory markers such as IL-10 and IFN-β in samples positive for anti-SARS-CoV-2 IgG. In conclusion, this research provides new insights into the complex interplay between immune responses to SARS-CoV-2 and influenza A virus in the Malaysian context. While SARS-CoV-2 antibodies do not significantly protect against influenza A virus replication, there is a noteworthy risk of ADE, and immune profile alterations that may impact disease progression. These findings highlight the need for continued surveillance in the era of overlapping respiratory virus epidemics and reinforce the importance of tailored vaccination strategies and public health interventions.

Initial

khm

Additional Information

Dissertation (M.A.) – Institute for Advanced Studies, Universiti Malaya, 2026.

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