 Okay, it's not going to be just me talking today. I'll then hand over to Yanni, Marta and Jenny to tell you a bit more about specific projects in our group. I'll just give you a brief overview of what we're doing. So at the heart of our research are vaccines for vulnerable populations and overcoming the dysfunction. So basically, by vulnerable populations, we're specifically interested in those chronic diseases and the aging population. With chronic diseases, we're focusing mainly on metabolic disease like type 2 diabetes and obesity. And really what we're trying to do is understand immune responses in these populations, how it compares to healthy people and how we can understand mechanisms and use that to design better vaccines or design new vaccines specifically targeted at these populations who are at higher risk of severe outcome form infection and also more susceptible to becoming infected in the first place. And we're studying all of this in three different areas which are highlighted on this slide. One of them is mediadosis, it's a neglected tropical disease prevalent in Southeast Asia and Northern Australia, caused by the crime negative intracellular bacteria buccalaurea sulimalae. The other one, also a big part of what we're doing is COVID-19, all of you know, caused by SARS-CoV-2. And we're part of two big consortia to investigate immune responses in the context of COVID-19. One of them is a national consortium called pitch, and the other one is international called sequel variants. And then finally, one of the new additions to our portfolio is identifying new vaccine candidates for AMR pathogens, including E. coli and Scythia lendemonia. So I'll start off with the COVID-19 work we're doing and just briefly introduce in the pitch consortium to you again. I've mentioned this last year, but just as a recap and for all of you who are new and introduction, the pitch consortium is a nationwide consortium led by Susie here in Oxford together with Paul Kleineman at the Peter Medeva building. And it consists of several sites across the UK, Newcastle, Liverpool, Sheffield, Birmingham and Oxford, also with involvement of UK HSA. And basically the aim is to really understand T cell or immune responses in healthcare workers to COVID-19. And it commenced at the start of the pandemic in April 2020. And since then, we've recruited over 2000 healthcare workers into this study. And just so you understand a bit better what the workflow of this is and how this looks, not just here in Oxford, but also in other sites. Basically, what we do is we invite healthcare workers to attend our clinics whenever they have a break for infection, but also close vaccine or pre-vaccine. And we're collecting longitudinal samples from these people in order to better understand the immune responses, the waning and the boosting of immune responses. So people are invited to the clinic, they attend either the JR hospital clinic or clinic or the Churchill hospital clinic. And then our nurses collect blood from them. And they also collect a thumb strip, which is basically just inserted into a nostril and collects the fluid inside your nostril. So we can actually get some data on mucosal antibodies as well. And these people are also provided with PCR nasal swab kits, which they can send in for PCR testing if they think they have break for infection. And then once the blood is collected, it comes down to the lab and our research system to process the bloods. And the components we're really interested in are plasma on top, which contains antibodies and other proteins of interest. And then this little fraction here at the interface, which contains all the important immune cells that we are interested in. And those are stored at ultra low temperatures for future analysis, functional analysis. So where are we up to with pitch at the moment? So we're tracking immune responses since 2020. And where this little star, the red star is, this is the time that we're currently looking at. So we're just about to collect the pre-v5 samples from people who will go on to receive the fifth dose. And this will be offered this week. I think we're beginning of next week to help her workers. And we're also collecting samples whenever people get break for infection. And so since the start of the pandemic, and that's the figure on the bottom left, we've been tracking T cell responses to SARS-CoV-2. And we can see that these are very well maintained. So the first gray dots, these are the baseline samples. And then you can see this nice increase after the first dose and a little bit more increase after the second dose. And then it's quite well maintained. It goes up slightly up and down a little bit, but really not, not much. And then also those responses are maintained in response to variants of concern like Omicron, VA1, VA2, which is also important for us to understand in terms of protection whenever new variants are coming in. Hey, so I'll hand over to Yanni. So hi everyone. My name is Yanni. I'm a second year DFIA student in this group. So I'm going to present some results for my project. So despite the widespread of SARS-CoV-2 infection, there are some people who reported that they never got infections. So I'm looking at their antibody and T cell responses. And to do this, I collected, our group collected samples from participants. The unexposed is people who are recruited early pandemic and like detected infections are people who got their breakthrough infections within the last 30 days. And the no known infection, these are people who self reported as never had infections in the beginning of pandemic. So to do this, I'm going to measure the, well, I measure the immune responses to spike protein, which is the component that present in the vaccines that's been deployed in the UK. And also measure the immune responses to other non spike proteins, including membrane, nuclear capsid, non structural protein and open reading frames. So for antibody, I use MSD platform. And for to measure the T cells, I use Ali spot and also the proliferation assay. So as we can see in this figure, people who have been vaccinated, this is a DI is people who just they got that breakthrough in vaccinated and got breakthrough infections after vaccination. And NKI is people who have been vaccinated and reported as never been infected. So as I expected, people who have been vaccinated have responses to spike protein. And, and here is nuclear capsid. So people who have breakthrough infection, they have responses to non spike proteins, which not present in the vaccine that they receive. While people who reported as never got infections, about 30% of those actually got respond antibody to nuclear capsid. So how about their T cell responses for T cell responses? As we can see here, unexposed people who are recruited early on pandemic, they don't have responses to spike because they're not vaccinated. And as expected, people are fascinated, they actually have T cell responses to spike. And about the other responses to non spike protein, similar to antibody people who reported. There are some people who actually have responses to non spike protein, and the DI are people who actually got breakthrough infection. So they have responses to other non spike proteins. So in this graph here, I just want to show like the proportion of responders. So the black one is people who are the unexposed people, as I expected, most of the time they not responded to spike or non spike, while people who got their breakthrough infection, they actually higher proportions in people who have spike and non spike. And next is people who started reported as never got infections. You can see like some of them actually have responses to non spike, which indicate that they may actually have like asymptomatic infections. So for at least what we can only measure like the interferon gamma secreting cells, and we cannot differentiate whether it is coming from CD4 or CD8. So using the proliferation, I say this is to differentiate whether the responses coming from CD4 or CD8. And again, as you can see, people are unexposed, they don't really respond that much. And the result here, we kind of see that people who started reported as never been infected seem to have like more responses, but also noted like the number of people, the sample that I have is actually much higher than a breakthrough infection. So this is still working in progress and I still need to add more data just to confirm this finding. So yeah, that is the result that I got so far. People who have been vaccinated, they have antibody antiseptic responses to spike proteins, and people who got breakthrough infections, they do have responses to non spike protein, which is very different from people who are unexposed. They don't have responses to non spike. So before I go, I also want to say just thank you to participants who actually volunteer for my study. I know some of you are actually here in this room. So thank you so much. Or even that people who actually express their interest to volunteer. So yeah, thank you. Hi. So my name is Marta. I am a postdoc in Susie's lab and I will be going through very briefly two projects that I've been involved in. The first one that has been mentioned a few times is the Seco variants project, which is a Southeast Asia initiative to combat SARS-CoV-2 variants. It's a collaborative study between three countries in Southeast Asia, Vietnam, Indonesia and Thailand, and experts at the University of Oxford, which are listed here. And it's led by Professor Ton in Vietnam. So as we know that viruses do mutate, and SARS-CoV-2 has shown a number of mutations since the beginning, starting with Wuhan, going to, for example, Delta and then Omicron, and Omicron leading to the rise of XBB 1.5 and XBB 1.16, which are shown here. And since then, there has been also other developments and variants that have come about. And we're interested in these because mutations can often lead to affect viral fitness, making the virus more transmissible, causing more severe disease or giving it the ability to evade our immunity. However, this is in the case with all variants, and we know that some of them have faded away, but in an ideal situation, we want to know as soon as a new variant arises, how fit is it, and will it affect or will it have a significant impact in the public? So the aim of this study is to develop and apply a multidisciplinary research platform in Southeast Asia for rapid assessment of the biological significance of SARS-CoV-2 variants, thereby informing a coordinated local and regional, as well as global response to COVID-19 pandemic, and to use this platform for future outbreaks and to use it for other pathogens as well. This is quite a busy slide, so I will just mention it briefly to show you the study design, which involves the use of already stored serum and cells, which have been stored pre-pandemic as well as the initial phase of the pandemic and which currently is also ongoing with the newer variants. The use of the genome of the virus that have been sequenced, still again, we continue to sequence the new variants and use that information. And from that, we will develop or design peptide libraries, which we could use for laboratory tests to look at T-cell responses, look at neutralizing antibodies from the plasma, and based on the laboratory findings and together with the clinical situation of these viruses, we hope to define the variants which have biological significance, and then this will be communicated to experts in health policy to have the appropriate impact. So the project has a significant component of capacity building, which has been taking place. So you have already seen the slide where Priyanka is giving training in Vietnam. We have had a student, a PhD student who visits us from Thailand who spent about six months in our lab working on T-cell responses. And we now have also two PhD students with whom we have met already today doing their PhDs in Oxford from Indonesia. And the project continues apparently. So that's it for this one. And then the second project that I would briefly mention is on antimicrobial resistance. It focuses on identification of new vaccine candidates for two of the pathogens that cause AMR. It is at the stage of the pump priming stage supported by these agencies. And the PI in this project is Vicky, who has an addition to the first two fundings who has recently received funding from VAC, the VAC to continue this project. The aim of this project is to identify new vaccine and therapeutic candidates for E.coli and Canemonia, which are two amongst the highest prevalent bacteria causing AMR. These are two of them. By screening patient cohorts for antibody and T-cell responses to key virulent factors. So the participants will include cohorts from UK as well as Vietnam. And these are patients who have bloodstream infection caused by E.coli and Canemonia as well as healthy controls from both countries. And the design for this project involves selecting target proteins through the literature search and available database, which Vicky has already done. And then manufacturing the proteins, which for some extent has already been done. And then after that we will screen for immunogenicity in our lab by looking at interfering gamma, early spot T-cell responses and ELISA to look for antibody responses. And finally, the analysis will include comparing the immune responses between bacterium with patients and healthy controls in the two countries, as well as the difference between the UK and Vietnam and explore if the disease severity survival are associated with the immune responses they have for these selected proteins. And I'm just going to give you a really brief update on two projects that I think Barbara talked about last year. So I'm Susie's project manager for her Meliodosis work. And this is Melvac One, which is going to be our phase one clinical trial and the first ever clinical trial of a Meliodosis vaccine. And it's definitely been a bumpy road getting to the point of starting and we're really hoping to kick off next year. And I think COVID of course has been a challenge and a lot of resources were directed to that, not internally in the group, but globally in terms of components for vaccines. But also another challenge is there's quite a lot of components going together to be mixed and delivered to the participants. So the vials in the top corner there, there's going to be a Hapsular Polysaccharide Protein Conjugate and then another antigen from the Bercalderia Bacterium, a protein HTP1 and then also mixed together with two adjuvants. So getting all those different parts together is taking its time, but we're making good progress. And then we're straight on to the second project, which is something we've been working on a lot in the meantime, with partners in Moru that carrying out a lot of the work and been really busy with this, surveying attitudes. Well, several parts to it were coming up on the next slide, talking to people about their awareness of Meliodosis as a problem, their attitudes towards vaccinations in general, and also taking part in vaccine trials because in Ubon Ratatani, the site where we're carrying out this project is not an area where vaccine trials are typically carried out, perhaps most people won't be exposed to that at all. And like in Oxford where I know a lot of you will have been bombarded with adverts to take part in clinical trials all the time. So yeah, asking people about their perceptions and willingness to take part in a future trial, because obviously after the phase one of the Meliodosis vaccine in Oxford, the next stage is to go to endemic areas. So just with through, we've got some, quite a lot of interviews have taken place, still some more to go, but we've got some early themes that have started to arise about how different age groups receive their information about disease outbreaks and vaccination, some more outward looking and some more passively received information. And we've had some really positive responses about a mixture of responses, but some really positive responses about taking part in trials and quite nice to see some, yeah, a good mixture of responses to that.