 Welcome to the Stop COVID-Dets webinar series brought to you by the University of the Philippines. The Stop COVID-Dets shorts make it easier for you to go to the presentations that you are interested in. I'm Dr. Raymond Sarmiento, Director of the National Telehealth Center. And I'm Dr. Susy Pineda Mercado, Adjunct Faculty of the National Telehealth Center. Together, let's stop COVID-Dets. True love lasts forever. Toto ba yan? May forever nga ba? Well, for some, yes. But immunity to COVID-19 vaccines will not last forever. Sorry, ah. Anyway, but let me define first at least these two terms, the primary series of vaccines versus the booster. By primary series of vaccines, we mean the dose and number of doses determined usually during clinical trials. Ito po yung data that will show na ito yung optimal. So the series of vaccine doses, pwede yung one lang or two to four doses, mahabano yung four, to reach full effectiveness of these vaccines. So if you remember or if you know, my children kayo, grand children, ang OPV for polyo requires three doses, MMR two doses, yung flu vaccine, but for the COVID vaccines that we have available right now, isa lang pwede yung merong one dose na binibigay and all others will require two doses. So now, we move to defining what is a booster dose, at least for this presentation, we refer to a third dose or additional dose to the primary series. So nabigyan na nung nando na, nag-load, alawa, then we add another one. So for some vaccines, a booster dose is needed months or years after the primary dose to refresh the immune system's memory and maintain protection. So ito mga naka-examples po dito, merong po talaga mga booster doses yan, but for COVID-19, do we need boosters? Masasagot po natin yan mamaya. So just to give you an idea, ito po yung four routine vaccines. Mahikita nyo, may mga cheetah, ilang doses ba yan? And then after so many months or many years, you have boosters. Kasi partial protection or maybe even no protection yet after one dose, which we just call priming dose, two to three dose primary series, and then you get higher or full protection after completion of what we call the primary series, but which will vary for different vaccine antigens. Okay. So let us understand why some will require boosters, others will not. So there is individual variation in immune response to vaccination. So I have listed here a number of these factors. So ang unong-unong siguro is intrinsic host factor, show age. Tino ba ang mas madaling mga generate ng Indian response? The younger, the middle age or the older sex, na genetics of the immune response, then those who have comorbidities or are immunocompromised may have lower immune responses and then we do have our behavioral as well as nutritional factors. Now, this is only for children or may mga factors din to consider. Among the extrinsic factors, we also have to consider, for example, pre-existing immunity. In the case of COVID, we have to look at natural immunity nung na COVID and then do we give vaccine pa ba or what do we do? And then these are for the host factors. These are for vaccine and administration factors. So we have to look at different vaccine types, the product, the vaccine itself, kumero silang adjuvant or what the dose, yung concentration of antigen in that formulation. And then the number of doses in the primary series and especially the interval between doses. You will see later, two weeks ba ang interval between the first and second doses? May three weeks, may four weeks, may eight to 12 weeks, may nilong pang ibang vaccines, not for COVID. Five to six months or longer. So these factors will make your immune responses vary. So iba-iba. So we're looking at different equality and types of antibody responses. For instance, so may na tayong tinotaw na IGM, IGA, IGG, may na tayong neutralizing, versus na neutralizing antibodies. We also look at cell-mediated immunity. May na tayong T-helper, may na tayong killer or cytotoxic T-cells. Not just na quality, but we had to look at na quantity. Ganu ka dami yung elicit na immune response na nyo. For antibodies, we're always looking at tighter. So ito yung magnitude. Mas mataas na tighter, of course, better. And that translates to a longer duration of immunity which could be weeks, months or years. Now, this is something I will explain again some more later, but over time, n with two or three or four boosters or doses, there will be an increase. This is an immunologic phenomenon, or immunologic, based on immunologic principles. There will be increase in potency, avidity to yung total binding ng antibody sa lahat ng mga antigenic epitopes na isang virus, for instance, yung affinity maturation, nagmamatured din yung strength ng binding niya habang tumatagan yung interval from the time you get the vaccine, and increasing the breath of the immune response, meaning nagiging broadly reactive yung antibodies. Okay, siguro, I'll just explain in more detail what does dosage requirement mean. So yung number of doses kasi major ibanga, for primary immunization, example kudito is for COVID. So for one dose meron tayo yung yansen, this one dose may provide enough immunity and afford up to 70% protection. So you see this graph here, pag one dose, this is what sort of antibody response you will get. But for other COVID vaccines, they will require two doses, like Pfizer, Moderna, Sputnik, Sinova, Simutaba. Okay, baka may nakalimutan ako. So pag mag-second dose ka, that will shoot up, I will explain again, dahil meron tayo yung memory response, satisfactorily secondary response. So one dose versus two doses. The spacing between doses as I already explained earlier will also be important. So different vaccines use different schedules. Yung three weeks ang Pfizer and Sputnik, I think have yung interval of three weeks in the first and second doses. Ang four weeks apart ay yung Sinova, Moderna, po-vaccine, I think. And then AstraZeneca ang hasd data on the longest interval, four weeks to 12 weeks. So actually, AstraZeneca gave data on the higher levels of antibodies when the interval between the first and second doses was longer, up to 12 weeks. Actually, mayro pa silang ibang data na longer than 12 weeks na mas mataas pa yung antibody response. So thus, the need for booster doses after primary series will depend on the duration of immunity, which could win in months or in years. If short-lived immunity, we may need to be boosters. So ito yung patinotoro po sa mga estudianto, I think a lot of your healthcare workers here, you enter into the immunology class. So ito yung primary versus secondary immune response. Ito yung first exposure, first dose sa inyo. So we call that the primary response, which is short lasting, mabili siyang bababa. It is smaller in magnitude, mas mababa yung level of antibodies. But that is the time when the switch from what we call IGN to IGG would occur. So maguumpis na yung pinatawag natin memory response. So now when we give the second dose, yan yung secondary response. So mayro tayong na generate na memory cells from the first dose. So the memory cells developed from primary response are activated very quickly. So makikita nyo dito in a, siguro a few days, five to seven days, papa nikagad yung mga antibodies niya. Mabilis ang response na yan. So faster response, also more pronounced, makikita nyo, mas mataas, taas, taas ng taito, higher magnitude or taito of antibodies at mas mataas, noong gerang duration ng immunity. And repeated exposure, you may have a second, a third, a fourth, leads to faster, stronger response, more effective at limiting the infection. Yan mga antibodies na yan. Sambaga leg, no? They come from the B cells which become plasma cells. So this is a little technical, but what I want you to appreciate here is ito mga antibodies na to galinga sa B cells. So the level of antibodies you get will depend on how many B cells divide into so many plasma cells later para to produce those antibodies. So mayan tayong tinatawag na clonal expansion. Ito yung clone ng nga re against one antigen of the COVID, of the spike, for instance, mag-clonally expand yan so dadami. Ito sabi ng clonal expansion, yung isa, yung isang B cell magiging galawa, yung galawa magiging apa, twalo. It is exponential. Then as you go along, so, ba una ang dito yung recognition. Marerecognize mo na ng B cell yung antigen, let us say the spike. Then ma-activate siya to clonally proliferate, dadame. Kaya din ay nyo, padami ng padami yan, expand ng expand. And what we have seen is more B cells clonally expand with time and with longer interval between doses. So more plasma cells will be there, will be dividing, and therefore the plasma cells are the ones producing the antibodies. And as you go along, hanggang tumatagal yung time na yung, merong tinatawag na affinity maturation. So parang di sa tao, habang nag-mama-mature, nag-tatagala. Yung affinity of binding of the antibody to the viral antigen and the manager generate the memory. So you see sabi ko, more antibodies produce stronger affinity. Therefore, there is wisdom in waiting for the right time to boost. Hindi po pwede, agad-agad. Yeah. This is another may detective or this is light, but what I want also you to understand is ito po mga vaccines natin, usually ang meron tayo, either the whole, virus, inactivated vaccine or the spike. But within the spike alone, marami poong tinatawag na B-cell antigenic epitopes. So hindi lang po isa yan, marami yung. At ang araw yan, kaya nga po, nagkakaroon ng immune evasions or variants, kasi na iibah yung mga antigens na yung dahil do sa mga mutations na yung. But without the mutations mo na, there are so many such B-cell epitopes, so marami. And that means, ito na, there are so many depicted here by different colors of antigens. And for each antigenic epitope, there will be an antibody that will be generated against that. So this is a very good article that was recently published as a print, pero towantawa kasi actually there are many such publications on other vaccines. What this is showing here is ito yung wang et al just released September 5. The profiles of antibodies from those who received three doses, those who received two doses, and those who had your antibodies after they recovered from COVID with yung convalescent sira. So these antibodies were dissected very, very comprehensively. So what did that show? Doon sa after the third dose, nito napapakita yung mga two doses, yung naka-received ng third dose, they produce a highly sifted humoral immune response. So merong po na e-evode na antibodies, yung ka sabi ko nga, ay ba yung mga antibodies na yung? That showed better neutralization drug, so mga as marame, especially also seen against the variance of concern. They also of course showed quick memory response and yung higher titer dahil boosting long lasting immune response in warding of COVID-19. So actually they were able to analyze, napakarami po nito, hindi top madalin ianalyze, 171 complex structures of SARS-CoV-2 neutralizing antibodies which identified ito, kung maray ito, iba ibayon zila. Identified structure activity correlates, so yung nakakabit na mga antigen at antibody pinag-aralang pumabuti ang, that revealed very potent variant of concern, resistant and broad-spectrum antigenic patches. So ito po ay medyo technical, pero ito po atitotorong atin sa immunology sa graduate school. Telaga po yung mga antibodies ay na iba-iba over time. There is a lot of memory B-cell clonal turnover. So yung siguro yung antibody composition changes in the B-cell repertoire which is driven by prolonged, repeated antigenic stimulation such as what you will find after a serb dose or an additional dose. So given that to boost or not to boost that is the big question. Angan ngayon, balika natin, ito na dito na kayo. Some of you may have received one dose. Some of you may have received two doses. So ito immune response better. Sinabi po na that the interval the longer the interval between the two doses better. But pignanin nyo kung yung second dose nyo pababana umas mababa pa then you have to consider a booster. Then there you have some considerations for boosters so waning immunity ba? We are loping at race groups sila yung talagang mas malimit maaga, magwain ng immunity the elderly the immunocompromise but not just the waning immunity but those are very high exposure risk. Yung mga talagang to meeting yung mga COVID patients or yung mga frontliners kailangan makita lahat yun. Then we have to look at the epidemiology of breakthrough cases over time and the disease, severity so pang may mga variance then performance we also have to look at the data nung mga vaccines for COVID. Kumaya data sila on how they will perform or have performed so yung looking at the safety and immunogenicity not just the immunogenicity do mommy ba yung antibody but is a third dose safe titignan din po natin nga and then ready bang magmix and match and you mix and match yung first first two doses are one platform and then the booster the third would be another platform and then there are also recent studies on dose sparing or lower doses given as boosters for instance na yung isan vaccine kilang kalahati lang nung dose na binibigay sa primary series ang binigay sa booster and that was also very good so question is what is the optimal timing for boosters is it 6 months 8 months 12 months it will depend so sorry na medyo anti-climatic ang aking ang aking last slide but despite saying all that we have to remember that the WHO official say that the scientific justification for boosters remains anti ang dami po dapat tino-consider so director general Tedros acknowledge that third doses might be necessary for at-risk groups but he said we do not want to see widespread use of boosters for healthy people and who are fully vaccinated the WHO target is for all countries to vaccinate at least 40% of their people by year's end and in fact the WHO called for a global moratorium on booster doses at least na initially until the end of September lapit na puno ang pero ang bababa parin ang global immunization coverage so this was later moved to end of 2021 to prioritize vaccinating the most at-risk people around the world who are yet to receive their first dose and just to give you an idea of the countries who are planning on giving boosters or are already giving boosters we have listed Israel nasa third dose ila although narin nito gusto pa nila mag forth dose US UK Czech Republic Germany France Thailand Indonesia China Cambodia so with that we hope that you learn this much as we did from that excellent presentation we also hope that you will join us every Friday from 12 noon to 2pm manila time on zoom facebook or youtube so stay safe stay connected and see you online