Sunday, March 26, 2023

What Is The Immune Response To Vaccination

Prevention Of Infection Versus Disease

Vaccine produces immune response, AstraZeneca says

In the case of the current pandemic of the virus SARS-CoV-2, a vaccine that prevents severe disease and disease-driven hospitalization could have a substantial public health impact. However, a vaccine that could also block acquisition of the virus, and thus prevent both asymptomatic and mild infection, would have much larger impact by reducing transmission in the community and potentially establishing herd immunity.

Two Types Of Vaccines

There are two major types of vaccines, live and non-live. Live vaccines contain the disease organism in a weakened form. They create a mild natural infection in the body, usually so mild that there are no symptoms. These vaccines give good protection against the disease they were designed for from the first dose.

Non-live vaccines contain the killed disease organism or parts of it. They are not very good at stimulating the immune system and usually have to be given with a helper substance, known as an adjuvant, and in several shots to give disease protection. The non-live vaccines can never create the real disease, so most doctors prefer them over live vaccines.

We have now investigated four live vaccines and six non-live vaccines, in Guinea-Bissau and other low-income countries, as well as in Denmark. A consistent pattern has emerged. The live vaccines reduce death and disease much more than can be explained by the specific protection. But the non-live vaccines, in spite of protecting against the vaccine disease, are associated with negative effects on health, including death, particularly for girls. Here are two examples.

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Multiple Vaccines Overwhelm Immune System Another Myth Debunked

There are a large number of tropes and myths pushed by the anti-vaccine crowd. Like toxic chemicals in vaccines. Or vaccines cause autism. And one that keeps showing up multiple vaccines overwhelm the immune system.

And like other articles Ive written about anti-vaccine myths and tropes, the idea of multiple vaccines harming children is easily debunked by scientific facts. And were doing that right here.


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Why Do Some Vaccinated People Still Get Infected

Following vaccination, some people may experience breakthrough infection where they still get the virus or illness despite being fully vaccinated. This is more likely if high levels of viruses are circulating in a population, or if certain viral variants are particularly contagious.9,10 No vaccine is 100% effective so some breakthrough infections are expected. Importantly, they dont mean the vaccine isnt working. The role of many vaccines is to prevent serious illness and death, not infection altogether.11 If breakthrough infections do occur in vaccinated people, the symptoms are usually less severe and may result in fewer hospitalisations and deaths than infections in those who are unvaccinated.10,12

If I Feel Sick After My Shot Does That Signal Strong Immunity

Vaccines: The Short on Shots

Scientists havent identified any relationship between the initial inflammatory reaction and the long-term response that leads to protection. Theres no scientific proof that someone with more obvious side effects from the vaccine is then better protected from COVID-19. And theres no reason that having an exaggerated innate response would make your adaptive response any better.

Both the authorizedmRNA vaccines provided protective immunity to over 90% of recipients, but fewer than 50% reported any reaction to the vaccine and far fewer had severe reactions.

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The Immune Response Following Vaccination

Schematic representation of the immune response and its age-related alterations following vaccination. Protein antigens administered together with adjuvants induce the activations of innate immune responses at the site of injection. The antigen is taken up by antigen-presenting cells , such as macrophages and dendritic cells . The local innate immune response facilitates maturation of DCs, which present stable major histocompatibility complex/peptide complexes . Mature DCs migrate into lymph nodes , where they induce activation and clonal expansion of naive CD4+ and CD8+ T cells. The activation and differentiation of naive B cells is induced by antigen and CD4+ T cell help . Naive B cells differentiate into memory B cells and antibody-secreting B cells . Long-term immunity is assured by memory B and T cells in the blood and lymph nodes, as well as by long-lived plasma cells and memory T cells in the bone marrow .

Protection From Reinfection In Cohort Studies

Multiple studies have compared the incidence of reinfection and primary infection during a specific time period to evaluate the level and duration of protection provided by initial infection with SARS-CoV-2. Table 2 summarizes data from seven observational cohort studies from six countries, each with > 10,000 participants, assessing the risk of reinfection over time. Five studies used RT-PCR positivity to define initial infection. In these studies, primary RT-PCR-confirmed SARS-CoV-2 infection decreased risk of subsequent infection by 8093% for at least 69 months . Studies specifically assessing persons seropositive with anti-N and anti-S antibodies following infection found slightly higher protective effects . Most studies had a mean or median follow-up period of approximately 7 months the longest reported follow-up was 12 months post-infection . Three studies included sub-analysis to assess if the protection waned over time none of these found a decline in protection within the follow-up period .

Of note, these studies occurred when the ancestral strain and Alpha variant were the predominantly circulating variants. There is evidence that protection may decrease in the setting of more transmissible variants of concern and variants being monitored , as discussed below.

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Initial Immune Response To Infection

SARS-CoV-2 enters cells by binding to angiotensin converting enzyme-2 receptors on the cell surface via the viral spike protein. As described in the Antibody Testing Guidelines, currently available serologic assays measure both overall production of antibodies against SARS-CoV-2 antigenic targets and functional ability to neutralize the SARS-CoV-2 virus via virus neutralization or pseudovirus neutralization tests . The antigenic targets most frequently assessed include those to the spike protein, receptor binding domain of the spike protein and nucleocapsid core. IgM, IgA, and IgG isotypes may be developed against any of these antigens. As discussed below, serum binding antibodies to S and RBD and neutralizing antibodies have all been shown to correlate with protection against symptomatic SARS-CoV-2 infection.

The vast majority of persons with SARS-CoV-2 infection generate detectable anti-SARS-CoV-2 antibodies, with multiple studies reporting seroconversion rates of 90% or higher . One large population-based study reported a lower seroconversion rate of 76%, though, among those who did not seroconvert in this study, only 21% reported symptoms, and authors noted that only 34% had strong evidence of a true-positive PCR . Among individuals who seroconvert following infection with SARS-CoV-2, substantial heterogeneity exists, with a 200-fold difference in peak antibody titers noted in some studies .

Vaccine Type And How Its Delivered

Oxford coronavirus vaccine results ‘very encouraging’ as it produces immune response

Many COVID-19 vaccine candidates contain parts of the SARS-CoV-2 spike protein to stimulate protective immunity. However, there are many different ways of delivering these proteins to the body, and some may be more effective than others at stimulating your immune system.

For example, the Oxford vaccine combines the spike protein with another virus to mimic the actions of SARS-CoV-2.

Meanwhile, the candidate developed by the University of Queensland contains the spike protein packaged with another compound to stimulate the immune system.

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Some people will likely need a follow-up booster shot to ensure longer-lasting immunity.

We may also see some vaccines delivered as a nasal spray. This may elicit a more effective immune response to COVID-19 in the upper respiratory tract, including the nostrils, mouth and throat.

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What Is The Immune System

The immune system is a network of cells, tissues, and organs that work together to defend the body from harmful germs. When bacteria, viruses, and other germs invade your body, they multiply and attack. This invasion is called an infection. Infections cause the diseases that make you sick.

Your immune system protects you from the disease by fighting off the invading germs.

The Persistence Of Memory

Another critical component of vaccination is that it helps produce memory B- and T-cells that are specific to the virus. Like an army reserve force, these immune cells can be quickly activated in the future to produce antibodies to stop the virus from invading your body. And unlike antibodies, these cells persist. Once you stimulate memory cells for a particular antigen, they can remain with you for life, says Gruber. For some pathogens, however, memory cells can be short-lived.

But developing this tailored immune response is not immediate. For someone who has not been previously exposed to the pathogen, it can take typically a couple of weeks to mount sufficient antibody to provide protection, says Gruber. And sometimes people need to receive one or more additional doses of a vaccine, commonly known as a booster, to build a strong immune response.

For someone whos been given a vaccine, the next time they encounter the pathogen, the immune response is sped up. Thats the basis of vaccination. Before the pathogen can replicate in the body, you’ve got antibody generated to prevent that from happening.

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The Myth Of Antigenic Overload

An important parental concern is that vaccines might overwhelm their childrens immune systems. In a telephone survey in the USA, 23% of parents agreed with the statement Children get more immunizations than are good for them, and 25% indicated that they were concerned that their childs immune system could be weakened by too many immunizations. However, there is ample evidence to disprove these beliefs. Although the number of vaccines in immunization programmes has increased, the total number of antigens has actually decreased from more than 3,200 to approximately 320 as a result of discontinuing the smallpox vaccine and replacing the whole-cell pertussis vaccine with the acellular vaccine,. Vaccines comprise only a small fraction of the antigens that children are exposed to throughout normal life, with rapid bacterial colonization of the gastrointestinal tract after birth, multiple viral infections and environmental antigens. Moreover, multiple studies have shown that children who received vaccinations had a similar, or even reduced, risk of unconnected infections in the following period,,,. Looking at children who presented to the emergency department with infections not included in the vaccine programme, there was no difference in terms of their previous antigen exposure by vaccination.

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Hard To Find What Youre Not Looking For

Vaccine adjuvants

Vaccines have been used for centuries. So if they have such profound effects on the risk of other diseases, why didnt we discover this a long time ago? The short answer is that you cant discover what youre not looking for.

Everybody has been convinced that vaccines only affected the target infection, so their effect on other infections and overall health was not studied. So while there are many studies that show that vaccines have protective effects, there is no data that shows that vaccines only have protective effects.

It is time to change our perception of vaccines: vaccines are not merely a protective tool against a specific disease, they affect the immune system broadly. In the case of live vaccines, the immune system is strengthened. In contrast, non-live vaccines seem to have a negative effect on the immune system in females.

The latter finding is an obvious cause for concern, particularly since it would be undesirable to stop using, say, the DTP vaccine, as it protects against three severe diseases. Fortunately, there is something to do. It appears that if a live vaccine is given after a non-live vaccine, the negative effect of the non-live vaccine may be mitigated. So there is an urgent need for studies testing different sequences of live and non-live vaccines.

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The Immune Systemthe Bodys Defense Against Infection

To understand how vaccines work, it helps to first look at how the body fights illness. When germs, such as bacteria or viruses, invade the body, they attack and multiply. This invasion, called an infection, is what causes illness. The immune system uses several tools to fight infection. Blood contains red blood cells, for carrying oxygen to tissues and organs, and white or immune cells, for fighting infection. These white cells consist primarily of macrophages, B-lymphocytes and T-lymphocytes:

Vaccines prevent diseases that can be dangerous, or even deadly. Vaccines greatly reduce the risk of infection by working with the bodys natural defenses to safely develop immunity to disease. This fact sheet explains how the body fights infection and how vaccines work to protect people by producing immunity.

  • Macrophagesmedia icon are white blood cells that swallow up and digest germs, plus dead or dying cells. The macrophages leave behind parts of the invading germs called antigens. The body identifies antigens as dangerous and stimulates antibodies to attack them.
  • B-lymphocytes are defensive white blood cells. They produce antibodies that attack the antigens left behind by the macrophages.
  • T-lymphocytes are another type of defensive white blood cell. They attack cells in the body that have already been infected.

The Immunity And Virus Transmission After Vaccination

Since the first confirmed case of novel coronavirus in November 2019, the SARS-CoV-2 virus has spread rapidly worldwide. To bring this pandemic to an end, a large share of the world needs to be immunized against the virus, and the safest way to achieve this protection is with a vaccine. However, there is an important question left to be answered: What is the chance of transmitting the virus after vaccination? Therefore, in this part of this review, we tried to answer this question by discussing COVID-19 transmission from cellular and humoral responses after the first and second doses of different types of vaccines, VOCs, and advantages and disadvantages of inhaled and intramuscular COVID-19 vaccines.

According to Mallapaty , several vaccines have been shown to provide high protection against COVID-19 . In addition, much evidence has demonstrated that they can considerably reduce the risk of SARS-CoV-2 transmission. Concerning the protective effect, vaccinated individuals who become infected are up to 78% less likely to spread the virus to household members than unvaccinated people .

Additionally, vaccine administration routes have advantages and disadvantages in relation to virus transmission. Certainly, it should be noted that intramuscular COVID-19 vaccines, which are currently administered, have an important limitation: the lack of mucosal immunization, since the primary route for SARS-CoV-2 transmission is the respiratory mucosa in the respiratory tract .

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Booster Shots And Additional Primary Doses

A booster shot is for people who built enough protection after completing their primary vaccine series, but then that protection decreased over time. Everyone ages 16 years and older who is fully vaccinated can get a booster. Learn more about getting a COVID-19 vaccine booster shot.

An additional primary dose is for people who did not build enough or any protection from their primary vaccine series. This appears to be the case for some immunocompromised people who received Pfizer-BioNTech or Moderna COVID-19 vaccines.

Currently, moderately or severely immunocompromised people ages 18 years and older who completed their Moderna vaccine primary series should plan to get an additional primary dose 28 days after receiving their second shot. People ages 12 years and older who completed their Pfizer-BioNTech vaccine primary series should also plan to get an additional primary dose 28 days after receiving their second shot.

Box 1 A Brief History Of Vaccination

Oxford-AstraZeneca vaccine shows positive immune response in early study

Almost 100years after Jenner, the work of Louis Pasteur on rabies vaccine in the 1880s heralded the beginning of a frenetic period of development of new vaccines, so that by the middle of the twentieth century, vaccines for many different diseases had been developed as inactivated pathogen products or toxoid vaccines. However, it was the coordination of immunization as a major public health tool from the 1950s onwards that led to the introduction of comprehensive vaccine programmes and their remarkable impact on child health that we enjoy today. In 1974, the World Health Organization launched the Expanded Programme on Immunization and a goal was set in 1977 to reach every child in the world with vaccines for diphtheria, pertussis, tetanus, poliomyelitis, measles and tuberculosis by 1990. Unfortunately, that goal has still not been reached although global coverage of 3 doses of the diphtheriatetanuspertussis vaccine has risen to more than 85%, there are still more than 19million children who did not receive basic vaccinations in 2019 .

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Can Sick Children Receive Vaccines

Some parents might be concerned that children with acute illnesses are less likely to respond to vaccines or are more likely to develop severe reactions to vaccines than are healthy children. Alternatively, some parents might believe that children who are ill shouldn’t further burden an immune system already committed to fighting an infection. However, vaccine-specific antibody responses and rates of vaccine-associated adverse reactions of children with mild or moderate illnesses are comparable to those of healthy children. For example, the presence of upper respiratory tract infections, ear infections, fever, skin infections or diarrhea does not affect the level of protective antibodies induced by immunization.

Data on the capacity of vaccines to induce protective immune responses in children with severe infections are lacking. Although a delay in vaccines is recommended for children with severe illnesses until the symptoms of illness resolve, this recommendation is not based on the likelihood that the child will have an inadequate immune response to the vaccine. Rather, the reason for deferring immunization is to avoid superimposing a reaction to the vaccine on the underlying illness or to mistakenly attribute a manifestation of the underlying illness to the vaccine.

What Is Immune Profiling And Immunophenotyping


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