 There are so many COVID vaccines that have been approved. We know that these vaccines have different efficacy as shown in this table. Now all these vaccines despite having different efficacies have been approved. This concept I've dealt in another video known as efficacy threshold. The link for that video I have given in the description section below. You can check that out. But the subject of this video is to find out what are the factors which affect the vaccine efficacy. Well, there are various factors. Some can be related to the vaccine itself. Some can be related to the population in which the vaccine is being administered. What are known as host factors and some can be related to the system. So first let's see the factors related to the vaccine. See, any vaccine has two components. One is the antigen which we want to target and the immune response develops against this antigen. And the second is kind of a danger signal, a tag which we give a. It kinds of alert the immune system that, okay, there is some foreign antigen which has entered the body. So because of this danger signal, the immune response to the antigen is much better. Now all vaccines have this first component that is the antigen. And the second component varies in different vaccines. So first factor which affects vaccine efficacy is the type of vaccine. We know that there are various types of vaccine. There is a killed virus vaccine, example is co-vaccine. Then there is live attenuated vaccine. Then there are viral vector vaccines, example is Covishield. And then with the recent scientific venture, we also have mRNA based vaccines, example being Pfizer vaccine. Well, you see that the killed vaccines do not have these alerting or danger signal. And generally these vaccines elicit a lesser immune response. So for eliciting a strong response, they require addition of something extra, which is known as adjuvant. This adjuvant we will discuss in a short while. On the other hand, live attenuated vaccines have both. They have the antigen as well as the alerting signal. However, for COVID, we do not have any approved live attenuated vaccine because they are kind of dangerous. See, they are live virus, right, even though it is attenuated. So they need a lot of research. We have to be sure that the vaccine is safe. So obviously it requires more time and time is something which we do not have as far as COVID is considered. Then there are viral vector vaccines. Now, see, this viral vector based vaccines can induce strong immune response since the viral vector itself can attach to some sensors in the body like toll like receptor and activate the immune response better. So the vector itself is acting as an alerting signal. And as far as mRNA vaccines are considered, see, these are new vaccines and they have not been used previously for any other disease. But in case of COVID, we are seeing that they are activating the immune system in a much better way. So yes, there is both antigen as well as an alerting signal in this mRNA based vaccines. So basically how the vaccines are engaging the immune system determines their efficacy. Now, in case of killed vaccines, we spoke about adjuvants. The addition of adjuvants to the formula can enhance the magnitude of the immune response. So these adjuvants act as that danger signal, that alerting signal for the immune system. Not only that, the type of response also depends on the type of adjuvants. See, immune response after vaccination consists of B cell responses which produce antibodies and then there are T cell responses, basically cytotoxic T cells which kill the infected cells. So this is cell mediated immunity. Now the vaccine may either produce predominantly B cell response or the T cell response or maybe both. For COVID, we want activation of the both responses. Now, for the activation of these responses, there is another component coming into picture, that is the T helper cells. These T helper cells themselves are of two types, TH1 and TH2. TH1 cells produce interferon gamma and interleukin 2, which activates macrophages and T cells. This promotes the cell mediated immunity. On the other hand, TH2 cells produce interleukins like interleukin 4, 5 and 6, which activate the B cell responses. Anyways, the type of adjuvant which is added to the vaccine depends on which type of response we need. And as told earlier that for COVID, we need both types of responses. A common adjuvant which is added to the vaccines is ALM. But ALM actually promotes this side responses, that is the TH2-based responses activating the B cell responses. So if only random is added, then obviously the vaccine efficacy will be lower. But if another adjuvant like a CPG pattern antigen, which is basically a protein similar to proteins of the virus, it will elicit both higher neutralizing antibodies since ALM is there and also it will activate the cell mediated immune response. Okay, so that was all about the types of vaccines. Now, root of administration of the vaccine is also important. See, for pathogens like SARS-CoV-2, which enter via the respiratory tract and stays there for some time, won't it be best that our immune system releases certain antibodies which are there in the respiratory mucosa and capture the virus then and there itself, so that it is not able to enter the lungs and damages it? Well, there are certain antibodies known as IG antibodies which are released into the mucosa. But for this, we need to give the vaccine nasally through the nasal root. But for COVID till now, we don't have any vaccine which is given by nasal root. And because only a limited amount of vaccines can be given by this root, especially live-it-innovated ones. And as I told, there are no live-it-innovated vaccines for COVID. Also, it will require the availability of the inhalational devices for administrating the vaccine. Again, this will add to the expenses of the country, isn't it? Okay, apart from the factors related to the vaccine, there are factors which are related to the population. First is the presence of co-morbidities. Like we are seeing in the case of COVID that if certain co-morbidities are present like diabetes or hypertension, it may be that the vaccine has lesser efficacy. Secondly, it depends on the age of the person also. Vaccine may have different efficacy in different age groups. Then, time since vaccination is also important. As the time passes, the antibodies decrease in blood and the efficacy of the vaccine decreases. So, for that, boosted doses of the vaccine may be required. Then, the efficacy of a vaccine also depends on the system. Suppose if the system is not proactive in administrating the vaccine, so even if a person who is vaccinated, what will happen? He may be exposed to a lot of people who are not vaccinated. So, the force of infection or what we call the viral load will be more. So, in these cases, vaccine efficacy may be lower. See, the vaccine efficacy what is tested in a lab may be different from what happens at ground level. So, there is a particular term used for it, known as vaccine effectiveness. In lab-controlled conditions, it is known as vaccine efficacy. And in a ground level, whatever is the efficacy of the vaccine, it is known as vaccine effectiveness. Anyways, there is another factor which can affect vaccine efficacy is the maintenance of proper storage conditions. Like if the temperature is not maintained for storing the vaccine, then its efficacy will decline, isn't it? So, that's the reason that vaccines which require lesser storage demand, say supposed to be stored at temperatures of around 2 to 8 degree Celsius, generally enter into developing countries while that which require more storage demand, more expensive storage demand may not enter into these countries. So, these are the factors which affect vaccine efficacy, factors related to the vaccine, factors related to the population and factors related to the system. Well, thanks for watching the video. If you liked it, do press the like button, share the video with others and don't forget to subscribe to the channel Physiology Open. Thank you.