Long-term COVID-19 antibody responses following vaccination and infection

Established Supervisors: 

A/Prof. Francesca Fernandez < Francesca.Fernandez@acu.edu.au> 

Roger Lord

Project Description

The global viral pandemic caused by SARS-CoV-2 (COVID-19) has been the impetuous for the development of a number of different vaccines against this pathogen. This effort has included constructs which have not been used previously in the formulation of a vaccine. Different COVID-19 vaccines have been approved for use in Australia by the Therapeutic Goods Administration (TGA). In Australia approval has been provided for two doses of one of these vaccines and yearly boosters for the adult population. Individuals may have received the same vaccine for the first two doses but may have elected to receive a different formulations for boosters as variations to the virus have arisen. Guidelines provided by the Australian Technical Advisory Group (ATAGI) have changed repeatedly and influenced which COVID-19 vaccine different cohorts of the population receive and the timing between doses. These guidelines have included advice on vaccine type and dosing intervals changing several times since 2021. Additionally, routine measurement of antibody (Ab) titres (immunoglobulin G) to determine if seroconversion has occurred following vaccination is not performed in Australia. Clinical trials undertaken by the companies that produce these vaccines has shown that Ab concentration has been found to wane over several months following COVID-19 vaccination. The rate which antibody titres fall over this time period varies with the vaccine used. Additionally, this information largely only exists for vaccination done using one type of vaccine. The Ab response where different combinations of COVID-19 vaccines are used is largely unexplored. Limited data exists as what Ab titre might equate to adequate protection to prevent serious infection, hospitalisation and death. Even where Ab titres fall, if a significant initial response occurred then subsequent responses following infection should be more rapid due to immunological memory formed following vaccination. The rationale for booster vaccination is based entirely around Ab concentration following each subsequent inoculation to see if an Ab response has been generated and if the titre is increasing. No attempt has been made to correlate Ab titre following vaccination with level of protection and what titre is needed to prevent serious infection. Infection with COVID-19 also increases the protective response and this too needs to be considered with regards to booster vaccination. The process is further complicated by the emergence of COVID-19 variants. Available COVID-19 vaccines (e.g. Pfizer, Moderna and Novavax) were all constructed based on the spike protein from the original Wuhan strain of COVID-19. Mutations in this target mean Ab generated following vaccination may not effectively recognise other variants and compromise the protective response. This raises the question as to when booster vaccinations are required to maintain protection and if variations are needed to the vaccine construct to maintain the effectiveness. This study seeks to determine the concentration of IgG antibody (Ab) generated following COVID-19 vaccination (S-antigen) and/or infection (N-antigen) in ACU staff which comprise a varied Australian population (age, gender, ethnicity, health status) and where different types and combinations of available COVID-19 vaccines have been used. Ab titres will also be influenced if an individual is immunocompromised and/or if regular use of medications that suppress the immune system are used to treat a condition. Specific questions to be addressed from the study are as follows: • Did all vaccinated participants in the study generate an appropriate immune response. • Does Ab responses reflect the vaccine combination used and time since last vaccination. • Are antibody titres higher in all individuals who received mRNA vaccines. • Are falling antibody titres following vaccination a reflection of vaccine formulation. • What is the effect of COVID-19 infection and recovery on Ab titre.

Description of the research

This project is a continuation of an earlier Honours study undertaken by Kate Petersen (2022) which failed to reach statistical significance due to the limited number of volunteers that could be recruited in the time allowed and resources (ELISA plates) available. This study will boost the number of volunteers recruited to allow enough statistical power to determine outcomes and subsequent peer review publication. The study may also recruit volunteers who were involved in the original study and allow insight into changes in antibody concentration with time. This can be explored with booster vaccine history (S-antigen) and any response to infection with the virus during this time (N-antigen). Antibody measurement against S-antigen (vaccination) and N-antigen (infection with COVID-19) can be undertaken effectively because of a successful FHS small equipment grant (2023) which allowed for the purchase of enough ELISA plates to allow this to be undertaken. These plates have been in long-term cold storage waiting for an Honours candidate to complete this study. This on-going project is therefore at a critical point where a significant publication is possible covering antibody responses following COVID-19 vaccination and/or infection. This research project will expose the Honours candidate to techniques commonly used in clinical trials and for which there has been a significant increase in demand for in recent years in terms of employment. These include the ability to interact confidently with volunteers to gain both complete responses to medical history while also putting individuals at ease during blood sampling. The ability to process clinical samples and carry out ELISAs are required for any future employment in hospital pathology, clinical trials and research projects. Collectively these skills will improve the confidence of the candidate in preparation for entry in any of these fields.

Designing a protein-phenolic delivery system for omega-3 oils: Oxidative stability and digestibility

Established Supervisors: 

Dr. Bo Wang <Bo.Wang@acu.edu.au> and A/P Pre De Silva <Pre.DeSilva@acu.edu.au> 

Dr. Bo Wang A/P Pre De Silva Dr Bo Wang and A/P Pre De Silva are nationally and internationally renowned experts in food/nutrition science and chemical science, respectively. Their experience supervising previous and current Honours and HDR students ensures effective mentorship for this project. The interdisciplinary nature of this study also bridges biomedical and nutrition sciences at ACU, offering students opportunities to engage in cutting-edge research while broadening their future academic and career prospects.

Project Description

This project aims to develop an innovative system to co-deliver omega-3 oils and olive leaf phenolic compounds. Omega-3 oils will serve as the core material, while the protein and phenolics form a protective wall material to enhance oil stability. Bio-accessibility testing under a simulated digestive environment will assess nutrient release and effectiveness at the molecular level. By integrating nutrition and biomedical sciences, this research addresses challenges in food-based health interventions, with potential applications in reducing oxidative stress and promoting overall well-being. The findings will advance the understanding of functional food delivery systems at molecular and practical levels.

Description of the research

During the Honours internship, the student will engage in optional activities beyond the thesis to enhance HDR readiness. These include learning various advanced microencapsulation theories and laboratory-based analytical techniques, gaining experimental and data analysis skills, planning and performing simulated digestion experiments, and creating research translation materials to bridge scientific findings with industrial demands. Additionally, students will have opportunities to engage in discussions with supervisors' industry partners. These experiences, supported by the supervisory team’s expertise and established industry partnerships, provide valuable skills in research methodologies, industry collaboration and project management. It prepares the student for future academic and professional growth

Turning green in healthy ageing: exploration of novel seaweed compound in cognitive performance

Established Supervisor: A/Prof. Francesca Fernandez < Francesca.Fernandez@acu.edu.au> 
Emerging Supervisor: Prof. Lyn Griffiths

Project Description

With a demographic shift toward an ageing population, dementia is becoming a growing public health concern worldwide. Alzheimer’s disease (AD), the most common form of dementia, affects over 55 million individuals in the world, with an estimated 10 million new cases per year. Symptoms of AD vary throughout disease progression, starting from a preclinical phase (with apparition of amyloid plaques in the brain and inflammation in brain) to mild and moderate memory impairment. Both memory impairment and inflammation are also present during healthy ageing. In our previous genetic study, genetic markers in the DNA (molecule carrying all genes) in a case control cohort for AD, have been reported significantly associated with cognitive performance in both AD patients and healthy aged individuals (aged average 78 years old). These genetic markers were present in specific genes called Sirtuin (SIRT), able to modulate the chromatin. The chromatin corresponds with how the DNA (carrying all the genes from an individual) will be compacted or in a more relaxed form in the nucleus of the cells. This will have an effect on how some genes will be turned active or no (like a light switch). SIRT proteins modulate many aspects of chromatin biology, such as genome stability but as well play a critical role in major biological functions such as cell survival, metabolism, cardiovascular function, ageing and memory. In ageing context, SIRT levels have been reported lower when compared to younger adults in a previous study. Increasing evidence have reported the critical roles of SIRT proteins in both health and pathological conditions such as cancer and neurodegenerative diseases. Several randomized controlled trials have demonstrated that some modulating factors are able to change the levels of SIRT proteins in human samples, which impact major physiological function. For instance, SIRT inhibitors have been considered in the treatment of several types of cancer while SIRT activators were suggested as therapeutic targets for age-related disorders such as AD. Resveratrol, a stilbene subclass of phenolic compounds, found in several plants, including grapes, has been previously reported increasing SIRT activity in human cells. When tested in clinical trial, resveratrol improved cognitive function in participants; however, it had also significant adverse effects (for 2.5 g) such as nausea, vomiting, diarrhea and liver dysfunction when administered longer term. Consequently, it is important to continue searching for SIRT modulators with limited adverse effects. Ulvan, is a sulfated polysaccharide extracted from Ulva green seaweed species. Ulvan supplements have been reported to possess significant biological properties, such as antioxidant, anti-inflammatory and anti-hyperlipidemic. Interestingly, ulvans can increase the levels of SIRT 1 in human cell lines. Furthermore, sulfated xylorhamnoglucuronan, or “SXRG 84” supplement (extracted from ulvans) was reported to decrease the levels of inflammation in a human double blind clinical trial setting with no adverse effects. Research gap: Interest in natural therapy and recent findings on the implication of SIRT protein in ageing have led to considering the potential of seaweed supplement for modulating the levels of SIRTs in a human pilot study. Considering that seaweed supplement (SXRG 84) has been already administered safely to human (in the context of obesity) and that ulvans can increase the levels of SIRT in human cells, we will test the effects of SXRG 84 administration in a pilot cohort of healthy adult older adults for 6 weeks and investigate the effects of this intervention on memory performance (cognitive tests) and peripheral markers for SIRT and inflammation (ethics submitted).

Description of the research

The honours student involved in this proposal will acquire a large range of new research from different discipline including psychology, nutrition and biomedical sciences. These research skills include cognitive testing of participants, saliva collection and analysis of peripheral tissues collected. The honours student will be involve in the recruitment of healthy aged adults (n= 10 in total, aged over 65,english speaker and considered in good health with no diagnosed severe condition) will be invited to attend the research lab (for saliva sample and blood collection) and perform memory testing at baseline (prior starting treatment) and at 7 weeks follow up at ACU, on Brisbane campus. Our previous research project has used the same type of cognitive battery tests in a cohort of participants including Alzheimer ’s disease (AD) patients and healthy aged adults. Both peripheral tissues (saliva and blood collected by supervisor) will be further analysed for comparison of the levels of SIRTs (and their activities) and the assessment of inflammatory markers (Interleukin 1, 6, TNF alpha and NF Kappa B). The analysis of these samples will occur at the Institute of Health and Biomedical Innovation (IHBI) in a research lab led by Prof. Lyn Griffiths (co-supervisor). The honours student will be trained for current methodology used in proteomics in the research lab (including Western Blot, Nanodrop, colorimetric essays). In addition, the honours student will be trained to deliver cognitive testing including Mini- Mental State examination (MMSE, assessment of global functioning), National Adult Reading Test (NART, testing working memory), Rey Auditory Verbal Learning (Recall memory), Controlled Oral Word Association Test (COWAT, testing of verbal fluency), Digit Span (working memory and executive function), Digit Symbol Coding (assessment of processing speed) and Boston Naming Test and Clock Drawing Task (spatial memory). The seaweed SXRG 84 supplement (Sulfated xylorhamnoglucuronan-rich extract) has been prepared by our industry partner Venus Shell System Pty Ltd (NSW), who will be part in future grant application and supervision to HDR student in the future. This supplement will administrated to participant by mixing it with food (2g/day) for 6 weeks (as previously used safely in clinical trials in obesity). Improvement of cognitive performance, increase of SIRT levels and their activity as well as a decrease of tested inflammatory markers in saliva and blood, are expected to be observed in the participants following the 6 week -SXRG 84 supplementation. This innovative project will provide an essential proof of concept for our research paradigm and design prior to progressing to future clinical trials and grant application (Medical Research Future Funding, Dementia and Aged care scheme) including AD patients in 2025. The pilot study undertaken by the student is crucial as it will demonstrates the feasibility of the study in a healthy elderly cohort prior progressing to AD patients. The honours student will acquire multi-disciplinary research skills (neuropsychological testing and biomedical analysis), at ACU and at IHBI, offering cutting-edge research equipment. This study will also contribute to provide training for a driven student who will undertake a Ph.D in 2026. This Ph.D will occur in collaboration with Industry Partner Venus Shell Systems (NSW) and collaborator Prof. Lyn Griffiths from IHBI (Queensland University of Technology). The Honours student will participate to produce multidisciplinary data (psychology, nutrition and biomedical science study) which will be published in high rank journal (Molecular psychiatry journal). This study will not only participate to the research excellence at ACU but as well may potentially affect positively vulnerable community.