Vaccines- Definition, Principle, Types, Examples, Side Effects

Vaccines are one of the most important and effective tools to prevent and control infectious diseases. Vaccines can protect individuals and communities from serious illnesses caused by bacteria, viruses, parasites, and other pathogens. Vaccination is the process of administering a vaccine to stimulate the immune system to produce antibodies and memory cells that can recognize and fight off the specific pathogen in the future. Vaccination can also reduce the spread of diseases by creating herd immunity, which means that when a large proportion of a population is immune to a disease, the chances of transmission are reduced.

Vaccination has a long and successful history of saving lives and improving public health. According to the World Health Organization (WHO), vaccination prevents 2-3 million deaths every year from diseases such as measles, polio, tetanus, diphtheria, pertussis, influenza, and hepatitis B. Vaccination has also led to the eradication of smallpox, the elimination of polio in most regions of the world, and the reduction of many other diseases that used to cause widespread suffering and mortality.

However, vaccination is not without challenges and limitations. Some diseases are difficult to develop effective vaccines for, such as HIV, malaria, tuberculosis, and herpes. Some vaccines require multiple doses or boosters to maintain immunity. Some vaccines may have side effects or adverse reactions in some individuals. Some people may have medical conditions or allergies that prevent them from receiving certain vaccines. Some people may have religious, ethical, or personal objections to vaccination. Some people may lack access to vaccines due to poverty, conflict, or lack of infrastructure.

Therefore, it is important to understand how vaccines work, what types of vaccines are available, what benefits and risks they entail, and what factors influence their development and delivery. In this article, we will explore these topics in detail and provide examples of some common vaccines and their effects. We will also discuss some of the current challenges and opportunities in vaccine research and innovation. By the end of this article, you will have a better appreciation of the role of vaccines in preventing and controlling infectious diseases and improving global health.

A vaccine is a biological preparation that stimulates the immune system to produce antibodies and memory cells against a specific disease-causing agent, such as a virus or a bacterium. Vaccines can prevent or reduce the severity of infectious diseases by enhancing the body`s natural defense mechanisms. Vaccines are usually administered by injection, but some can also be given orally or nasally.

The concept of vaccination dates back to ancient times, when people observed that survivors of certain diseases were immune to subsequent infections. For example, in China and India, people practiced variolation, which involved exposing healthy individuals to material from smallpox pustules to induce immunity. However, this method was risky and sometimes fatal, as it could transmit other diseases or cause severe reactions.

The modern era of vaccination began in the late 18th century, when Edward Jenner, an English physician, discovered that cowpox, a mild disease affecting cattle, could protect humans from the deadly smallpox. He inoculated a young boy with cowpox pus and later exposed him to smallpox, demonstrating that he was immune. Jenner called his method vaccination, from the Latin word for cow, vacca. His work paved the way for the development of other vaccines against diseases such as rabies, cholera, typhoid, anthrax, and plague.

The 19th and 20th centuries saw major advances in vaccine science and technology, such as the use of attenuated (weakened) or inactivated (killed) pathogens, the isolation of specific antigens (molecules that trigger an immune response), the development of recombinant DNA techniques (which allow the insertion of genes from one organism into another), and the discovery of adjuvants (substances that enhance the effectiveness of vaccines). These innovations led to the creation of vaccines against diseases such as polio, measles, mumps, rubella, hepatitis B, influenza, meningitis, and human papillomavirus (HPV).

Vaccination has been one of the most successful public health interventions in history, saving millions of lives and eradicating or controlling many infectious diseases. According to the World Health Organization (WHO), vaccination prevents 2-3 million deaths every year from diseases such as diphtheria, tetanus, pertussis (whooping cough), and measles. Vaccination also contributed to the global eradication of smallpox in 1980 and the elimination of polio from most regions of the world. However, some challenges remain, such as vaccine hesitancy (the reluctance or refusal to accept vaccination), vaccine shortages or inequitable access, emerging or re-emerging diseases (such as COVID-19), and the need for new or improved vaccines against diseases that still cause significant morbidity and mortality.

Vaccines are biological preparations that are made up of killed or attenuated pathogens (virus or bacteria) or part of the surface of the antigen. The preparation is made in such a way that it can not cause disease on its own, but it helps the body to develop a memory type of immunity. This means that if an individual encounter or is infected by the same pathogen (whose part has been used to prepare the vaccine), the immunity will ‘remember’ and induce a more vigorous immune response against the pathogen.

Initially, the innate immune response (primary response) elicited on the first encounter with a pathogen, is normally slow and that is why one will display symptoms of the disease before the immune system can elicit a reaction to kill the pathogen, and therefore the body develops an adaptive immune response (secondary response) through specialized immune cells which counter the pathogen and create a long-lasting memory.

Therefore, vaccination or the introduction of a vaccine into the body will have a similar kind of immune reaction (secondary response) only that it will by-pass the slow initial response but enables the body to acquire immunity (from the vaccine). In other words, the vaccine tricks the body to believe that it has the disease, and therefore, able to fight the disease. This makes the body be able to kill the pathogen before it can have the chance to cause disease due to memory that is created from vaccination.

Vaccination is the safest and most common way to gain immunity against bacteria or viruses that your body has yet to encounter.

Generally, a vaccine works as follows:

• Administration of vaccine which contains antigens for a specific disease or pathogen
• Identification and recognition of the antigen in the vaccine as foreign, by the immune system
• Development of antibodies by the immune system to neutralize the antigens.
• Storage of these immune effector antibodies as memory antibodies for future response in case an individual is exposed to the live pathogen or disease.

Significantly, vaccination is done to prevent diseases and wipe them out in eventuality. Administration of a vaccine to a significant proportion of a population protects those who receive the vaccine as well as those who cannot receive the vaccine. This concept is called “herd immunity.” When a high percentage of the population is vaccinated and immune to a disease, they do not get sick — so there is no one to spread the disease to others. This herd immunity protects the unvaccinated population from contagious (spread from person to person) diseases for which there is a vaccine.

Vaccines are biological preparations that contain antigens from a specific pathogen or disease, and they are designed to stimulate the immune system to produce protective antibodies and memory cells. Vaccines can prevent or reduce the severity of infectious diseases, and some can also protect against cancer.

There are several types of vaccines, each with different advantages and disadvantages. The type of vaccine depends on factors such as the nature of the pathogen, the target population, the availability of technology, and the safety and efficacy of the vaccine. Here are some of the main types of vaccines and their characteristics:

• Live-attenuated vaccines: These vaccines use a weakened (or attenuated) form of the live pathogen that causes a disease. They mimic a natural infection and elicit a strong and long-lasting immune response, usually with one or two doses. However, they may also have some limitations, such as:

  • They may cause mild symptoms or revert to a virulent form in rare cases.
  • They may not be suitable for people with weakened immune systems or certain medical conditions.
  • They may require refrigeration and careful handling to maintain their potency.

  Examples of live-attenuated vaccines include measles, mumps, rubella (MMR), varicella (chickenpox), rotavirus, yellow fever, and oral polio vaccines.

• Inactivated vaccines: These vaccines use a killed or inactivated form of the pathogen that causes a disease. They are safer than live vaccines and can be used for people with compromised immunity. However, they may also have some drawbacks, such as:

  • They may elicit a weaker immune response than live vaccines and require multiple doses and boosters to maintain immunity.
  • They may not induce mucosal immunity or cellular immunity as effectively as live vaccines.

  Examples of inactivated vaccines include hepatitis A, rabies, injectable polio, and seasonal influenza vaccines.

• Subunit, recombinant, polysaccharide, and conjugate vaccines: These vaccines use specific parts or components of the pathogen, such as proteins, polysaccharides (sugars), or antigens produced by genetic engineering. They have several advantages over whole-organism vaccines, such as:

  • They are more specific and targeted to key antigens that induce immunity.
  • They are less likely to cause adverse reactions or contain unwanted contaminants.
  • They are easier and faster to produce in large quantities.

  However, they may also have some limitations, such as:

  • They may not stimulate a strong immune response on their own and require adjuvants (substances that enhance immunogenicity) or multiple doses.
  • They may not induce mucosal immunity or cellular immunity as effectively as live vaccines.

  Examples of subunit vaccines include hepatitis B, human papillomavirus (HPV), acellular pertussis (whooping cough), and meningococcal B vaccines. Examples of recombinant vaccines include HPV and hepatitis B vaccines. Examples of polysaccharide vaccines include pneumococcal and meningococcal A/C/W/Y vaccines. Examples of conjugate vaccines include Haemophilus influenzae type b (Hib), pneumococcal, meningococcal A/C/W/Y, and meningococcal B vaccines.

• Toxoid vaccines: These vaccines use inactivated toxins (toxoids) produced by certain bacteria that cause disease. They induce immunity against the harmful effects of the toxins rather than the bacteria themselves. They have some benefits over other types of vaccines, such as:

  • They are safe and stable and do not contain live organisms.
  • They can prevent serious complications or death from toxin-mediated diseases.

  However, they may also have some drawbacks, such as:

  • They may require multiple doses and boosters to maintain immunity.
  • They may not prevent colonization or transmission of the bacteria.

  Examples of toxoid vaccines include diphtheria and tetanus vaccines.

• Messenger RNA (mRNA) vaccines: These are a new type of vaccine that use synthetic mRNA molecules that encode the instructions for making a specific antigen from the pathogen. The mRNA is delivered into the cells by lipid nanoparticles and translated into proteins by the cell`s own machinery. The proteins then trigger an immune response against the pathogen. mRNA vaccines have several potential advantages over other types of vaccines, such as:

  • They are easy and fast to design and manufacture using standardized processes.
  • They do not contain any live organisms or foreign substances that could cause allergic reactions or infections.
  • They can induce both humoral and cellular immunity against the pathogen.

  However, they may also have some challenges, such as:

  • They require ultra-cold storage and transportation to maintain their stability.
  • They may cause local or systemic reactions such as pain, swelling, fever, fatigue, headache, or muscle ache in some people.
  • They have not been extensively tested for long-term safety and efficacy in large populations.

  Examples of mRNA vaccines include COVID-19 vaccines developed by Pfizer-BioNTech and Moderna.

• Viral vector vaccines: These vaccines use harmless viruses (vectors) that carry the genetic material of a specific antigen from the pathogen. The vectors infect the cells and deliver the antigen into them. The antigen is then expressed by the cells and recognized by the immune system. Viral vector vaccines have some advantages over other types of vaccines, such as:

  • They can induce both humoral and cellular immunity against the pathogen.
  • They can target multiple antigens at once by using different vectors or combining them with other vaccine components.
  • They can be administered by different routes such as intramuscular injection or nasal spray.

  However, they may also have some disadvantages, such as:

  • They may cause mild symptoms or immune reactions due to the vector itself.
  • They may be less effective in people who have pre-existing immunity to the vector virus.
  • They may pose biosafety risks if they recombine with other viruses or escape from containment.

  Examples of viral vector vaccines include Ebola vaccine developed by Johnson & Johnson, COVID-19 vaccine developed by Oxford-AstraZeneca, COVID-19 vaccine developed by Janssen/Johnson & Johnson, COVID-19 vaccine developed by Gamaleya Research Institute (Sputnik V), COVID-19 vaccine developed by CanSino Biologics (Ad5-nCoV), COVID-19 vaccine developed by Bharat Biotech (Covaxin), malaria vaccine developed by Sanaria (PfSPZ), HIV vaccine developed by GeoVax (GOVX-B11), tuberculosis vaccine developed by VPM1002.

  Whole-organism vaccines

Whole-organism vaccines are vaccines that contain an entire pathogen that has been either killed or weakened so that it cannot cause disease. These vaccines can elicit strong protective immune responses and many of the vaccines in clinical use today are prepared in this manner. However, not every disease-causing microbe can be effectively targeted with a whole-organism vaccine.

There are two main types of whole-organism vaccines: inactivated and live-attenuated.

Inactivated vaccines

Inactivated vaccines are produced by killing the pathogen with chemicals, heat, or radiation. The killed pathogen cannot cause disease, but it can still stimulate the immune system to produce antibodies and memory cells. One advantage of inactivated vaccines is that they are stable and safer than live-attenuated vaccines, as there is no risk of reversion or mutation to a virulent form. However, a disadvantage of inactivated vaccines is that they elicit a weaker immune response and therefore require more vaccine doses and booster shots to confer protective immunity.

Examples of inactivated vaccines include polio (Salk vaccine), rabies, typhoid, cholera, pertussis, pneumococcal, hepatitis A, and influenza vaccines.

Live-attenuated vaccines

Live-attenuated vaccines are prepared from a whole organism that has been weakened or attenuated in the laboratory so that it can no longer cause disease but can still replicate in the host`s body. These vaccines elicit strong immune responses that can confer life-long immunity after only one or two doses. They are also relatively easy to create for certain viruses, but difficult to produce for more complex pathogens like bacteria and parasites.

One disadvantage of live-attenuated vaccines is that there is a remote chance that the weakened germ can mutate or revert back to its full strength and cause disease, especially in people with weakened or damaged immune systems. Another disadvantage is that live-attenuated vaccines require refrigeration and protection from light to maintain their potency.

Examples of live-attenuated vaccines include measles, mumps, rubella (MMR), polio (Sabin vaccine), rotavirus, tuberculosis (BCG), varicella (chickenpox), yellow fever, and influenza (FluMist).

Chimeric vaccines

Chimeric vaccines are a type of live-attenuated vaccine that contain genetic information from and display biological properties of different parent viruses. They are created by modern genetic engineering techniques that enable the combination of DNA from two or more sources. Chimeric vaccines can potentially offer broad protection against multiple strains or types of viruses.

One example of a chimeric vaccine is a NIAID-developed vaccine consisting of a dengue virus backbone with Zika virus surface proteins. This vaccine is undergoing early-stage testing in humans.

Subunit Vaccines

Subunit vaccines are vaccines that contain purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response. Subunit vaccines can be made from dissembled viral particles in cell culture or recombinant DNA expression, in which case they are called recombinant subunit vaccines. A subunit vaccine does not contain the whole pathogen, unlike live attenuated or inactivated vaccines, but contains only the antigenic parts such as proteins, polysaccharides or peptides.

Subunit vaccines have several advantages over whole-pathogen vaccines, such as:

• They are safer and more stable than vaccines containing whole pathogens, as they cannot cause disease or revert to a virulent form.
• They are well-established technology and suitable for immunocompromised individuals.
• They avoid potential concerns of contaminants or unwanted proteins in vaccines based on purified macromolecules.
• They allow the production of sufficient quantities of purified antigenic components.

However, subunit vaccines also have some disadvantages, such as:

• They elicit a weaker immune response and may require the use of adjuvants and booster shots to confer protective immunity.
• They are relatively complex to manufacture compared to some vaccines.
• They require time to examine which antigenic combinations may work best.

There are different types of subunit vaccines based on the nature and source of the antigens, such as:

• Polysaccharide vaccines: These vaccines are prepared using the sugar molecules or polysaccharides from the outer layer of a bacterium or virus. They create a response against the molecules in the pathogen`s capsule. However, these molecules are small and not very immunogenic, especially in infants and young children. Therefore, they tend to be ineffective in this age group and induce a short-term immunity with no memory. To overcome this limitation, these sugar molecules are chemically linked to carrier proteins and work similarly to conjugate vaccines. Examples of polysaccharide vaccines include meningococcal and pneumococcal vaccines.
• Conjugate vaccines: These vaccines are prepared by linking the polysaccharides or sugar molecules on the outer layer of the bacterium to a protein antigen or toxoid from the same or a different microbe. The polysaccharide coating disguises a bacterium`s antigens so that the immature immune systems of infants and younger children cannot recognize or respond to them. Conjugate vaccines get around this problem by enhancing the immunogenicity of the polysaccharides through the linkage with a protein. This formulation greatly increases the ability of the immune systems of young children to recognize the polysaccharide and develop immunity. Examples of conjugate vaccines include Haemophilus influenzae type B (Hib), pneumococcal and meningococcal vaccines.
• Toxoid vaccines: These vaccines are prepared from inactivated toxins, by treating the toxins with formalin, a solution of formaldehyde and sterilized water. This process of inactivation of toxins is known as detoxification and the resultant inactive toxin is known as a toxoid. Detoxification makes the toxins safe to use. The toxins used for the preparation of toxoids are obtained from the bacteria that secrete the illness-causing toxins. When the host body receives the harmless toxoid, the immune system adapts by learning how to fight off the natural bacterial toxin responsible for causing illness, by producing antibodies that lock onto and block the toxin. Examples of toxoid vaccines include diphtheria and tetanus toxoid vaccines.
• Recombinant protein vaccines: These vaccines are produced by using recombinant DNA technology, which involves inserting DNA encoding an antigen such as a bacterial surface protein into bacterial or mammalian cells, expressing the antigen in these cells, and then purifying it from them. Recombinant protein vaccines allow the avoidance of several potential concerns raised by vaccines based on purified macromolecules, such as contaminants or unwanted proteins. The production of recombinant protein vaccines also allows the production of sufficient quantities of purified antigenic components. Examples of recombinant protein vaccines include hepatitis B, human papillomavirus (HPV), influenza and coronavirus disease 2019 (COVID-19) vaccines.
• Nanoparticle vaccines: These vaccines are based on a strategy to present protein subunit antigens into the immune system using nanoparticles, which are microscopic particles that can self-assemble into various shapes and display antigens on their surface. Nanoparticle vaccines can stimulate a broad and long-term immune response and overcome some of the limitations of conventional subunit vaccines, such as stability and delivery issues. Nanoparticle-based experimental vaccines are being evaluated for influenza, respiratory syncytial virus (RSV), Epstein-Barr virus and malaria infections.

Subunit vaccines are generally safe for injection and have minimal side effects compared to whole-pathogen vaccines. The chances of adverse effects vary depending on the specific type of vaccine being administered. Minor side effects include injection site pain, fever, fatigue, headache and muscle ache, which usually resolve within hours or days after vaccination. Serious adverse effects consist of anaphylaxis and potentially fatal allergic reactions, but they are rare and occur in 1 to 1 million people who receive subunit vaccines. The contraindications for subunit vaccines are also vaccine-specific; they are generally not recommended for people with a previous history of anaphylaxis to any component of the vaccine. Advice from medical professionals should be sought before receiving any vaccination.

Nucleic acid vaccines

Nucleic acid vaccines are a novel type of vaccines that use the genetic material of the pathogen, either DNA or RNA, to induce an immune response in the host. Unlike conventional vaccines that introduce a weakened or killed pathogen or a subunit of it, nucleic acid vaccines deliver the instructions for the host cells to produce the antigen themselves. This way, the antigen is expressed in its native form and can elicit a strong and specific immune response.

There are two main types of nucleic acid vaccines: DNA vaccines and mRNA vaccines.

DNA vaccines

DNA vaccines consist of a circular piece of DNA called a plasmid that contains the gene encoding the antigen of interest. The plasmid also has a promoter sequence that allows the gene to be transcribed in the host cells. The plasmid is introduced into the host by various methods, such as injection, electroporation, gene gun, or microneedles. Once inside the cells, the plasmid is transported to the nucleus, where it is transcribed into mRNA. The mRNA then moves to the cytoplasm, where it is translated into the antigen protein by the ribosomes. The antigen protein is then presented on the cell surface by the major histocompatibility complex (MHC) molecules, where it can be recognized by the immune system.

DNA vaccines have several advantages over conventional vaccines, such as:

• They are easy and cheap to produce and store
• They are stable and do not require refrigeration or special handling
• They can induce both humoral and cellular immunity
• They can be designed to target multiple antigens or strains of a pathogen
• They have a low risk of contamination or reversion to virulence

However, DNA vaccines also have some limitations and challenges, such as:

• They may have low immunogenicity and require multiple doses or adjuvants
• They may induce immune tolerance or anergy if the antigen is expressed at low levels or for a long time
• They may cause unwanted integration into the host genome or trigger autoimmune reactions
• They may face regulatory and ethical hurdles for human use

Some examples of DNA vaccines that have been developed or tested for human diseases include:

• Hepatitis B: The first DNA vaccine approved for human use in 2005 by the Chinese FDA. It is marketed as Heberbiovac HB and has shown to be safe and effective in preventing hepatitis B infection.
• HIV: Several DNA vaccines have been tested in clinical trials for HIV prevention or treatment, but none have shown conclusive efficacy so far. Some of them include VRC-HIVDNA016-00-VP, PENNVAX-GP, and AGS-004.
• COVID-19: Several DNA vaccines are under development or testing for COVID-19 prevention, such as INO-4800, ZF2001, and AG0301-COVID19.

mRNA vaccines

mRNA vaccines consist of a synthetic messenger RNA (mRNA) molecule that encodes the antigen of interest. The mRNA is encapsulated in a lipid nanoparticle (LNP) that protects it from degradation and facilitates its delivery into the host cells. The LNP is injected into the host, where it fuses with the cell membrane and releases the mRNA into the cytoplasm. The mRNA is then translated into the antigen protein by the ribosomes. The antigen protein is then presented on the cell surface by the MHC molecules, where it can be recognized by the immune system.

mRNA vaccines have several advantages over conventional vaccines, such as:

• They are easy and fast to produce and modify
• They do not require any viral or bacterial vectors or culture systems
• They can induce both humoral and cellular immunity
• They do not integrate into the host genome or cause any genetic alteration
• They have a low risk of contamination or reversion to virulence

However, mRNA vaccines also have some limitations and challenges, such as:

• They are unstable and require ultra-cold storage and transportation
• They may have low immunogenicity and require multiple doses or adjuvants
• They may cause adverse reactions such as inflammation, fever, or allergic responses
• They may face regulatory and ethical hurdles for human use

Some examples of mRNA vaccines that have been developed or tested for human diseases include:

• COVID-19: The first mRNA vaccines approved for human use in 2020 by several regulatory agencies. They are marketed as Pfizer-BioNTech COVID-19 vaccine (BNT162b2) and Moderna COVID-19 vaccine (mRNA-1273) and have shown to be safe and effective in preventing COVID-19 infection.

• Influenza: Several mRNA vaccines are under development or testing for influenza prevention, such as BNT162b1, CV8102, and ARCT-021.

  Side effects of vaccines

Vaccines are generally safe and effective, but they can sometimes cause mild or moderate side effects that usually go away within a few days. These side effects are signs that the immune system is responding to the vaccine and building protection against the disease. However, in rare cases, some people may experience serious or severe side effects that require medical attention or emergency care.

Some of the common side effects of vaccines include:

• Pain, redness, swelling, or itching at the injection site
• Fever, chills, headache, fatigue, muscle or joint pain
• Nausea, vomiting, diarrhea, or abdominal pain
• Swollen lymph nodes
• Rash or hives

These side effects can be relieved by applying a cold compress to the injection site, drinking plenty of fluids, resting, and taking over-the-counter pain relievers or antihistamines as directed by a health care provider . However, it is not recommended to take these medicines before vaccination to prevent side effects, as it is not known how they might affect the vaccine`s effectiveness.

Some of the rare but serious side effects of vaccines include:

• Anaphylaxis: a severe allergic reaction that can cause difficulty breathing, swelling of the face and throat, a fast heartbeat, a rash all over the body, dizziness, and weakness . This can happen within minutes or hours of getting a vaccine and requires immediate medical care. People who have had an anaphylactic reaction to a vaccine or any of its ingredients should not receive that vaccine again.
• Thrombosis with thrombocytopenia syndrome (TTS): a blood clotting disorder that can cause serious problems such as stroke, heart attack, pulmonary embolism, or death. This can happen within three weeks of getting the Janssen/Johnson & Johnson COVID-19 vaccine and is more common in women under 50 years of age. People who have had TTS after getting this vaccine or any other adenovirus vector vaccine should not receive that vaccine again.
• Myocarditis and pericarditis: inflammation of the heart muscle or the lining around the heart that can cause chest pain, shortness of breath, or irregular heartbeat. This can happen within one week of getting an mRNA COVID-19 vaccine (Pfizer-BioNTech or Moderna), especially after the second dose and more often in males aged 12 to 29 years. Most cases are mild and resolve with rest and medication. People who have had myocarditis or pericarditis after getting an mRNA COVID-19 vaccine should avoid getting another dose of any COVID-19 vaccine.
• Guillain-Barre syndrome (GBS): a neurological disorder that can cause weakness, tingling, numbness, or paralysis of the limbs, face, or other parts of the body. This can happen within 42 days of getting the Janssen/Johnson & Johnson COVID-19 vaccine, mostly in men aged 50 to 64 years. Most cases recover with treatment but some may have long-term complications.

People who experience any of these serious side effects should seek immediate medical care and report them to their health care provider and to the Vaccine Adverse Event Reporting System (VAERS) in the U.S. or the Canada Vigilance Program in Canada . These systems help monitor the safety and effectiveness of vaccines and identify any potential problems.

It is important to remember that the benefits of vaccination outweigh the risks for most people. Vaccines can prevent serious and life-threatening diseases that can cause disability or death. By getting vaccinated, people can protect themselves and others from these diseases and help stop their spread. Vaccines are tested for safety and effectiveness before they are approved for use and are continuously monitored for any adverse events after they are administered. People who have questions or concerns about vaccines should talk to their health care provider or visit reliable sources of information such as:

• Centers for Disease Control and Prevention (CDC) - Vaccine Safety
• Food and Drug Administration (FDA) - Vaccine Safety
• Health Canada - Vaccine Safety
• Public Health Agency of Canada - Vaccine Safety

Subunit vaccines are vaccines that contain purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response. Subunit vaccines can be made from dissembled viral particles in cell culture or recombinant DNA expression, in which case they are called recombinant subunit vaccines. A subunit vaccine does not contain the whole pathogen, unlike live attenuated or inactivated vaccines, but contains only the antigenic parts such as proteins, polysaccharides or peptides.

Subunit vaccines have several advantages over whole-pathogen vaccines, such as:

• They are safer and more stable than vaccines containing whole pathogens, as they cannot cause disease or revert to a virulent form.
• They are well-established technology and suitable for immunocompromised individuals.
• They avoid potential concerns of contaminants or unwanted proteins in vaccines based on purified macromolecules.
• They allow the production of sufficient quantities of purified antigenic components.

However, subunit vaccines also have some disadvantages, such as:

• They elicit a weaker immune response and may require the use of adjuvants and booster shots to confer protective immunity.
• They are relatively complex to manufacture compared to some vaccines.
• They require time to examine which antigenic combinations may work best.

There are different types of subunit vaccines based on the nature and source of the antigens, such as:

• Polysaccharide vaccines: These vaccines are prepared using the sugar molecules or polysaccharides from the outer layer of a bacterium or virus. They create a response against the molecules in the pathogen`s capsule. However, these molecules are small and not very immunogenic, especially in infants and young children. Therefore, they tend to be ineffective in this age group and induce a short-term immunity with no memory. To overcome this limitation, these sugar molecules are chemically linked to carrier proteins and work similarly to conjugate vaccines. Examples of polysaccharide vaccines include meningococcal and pneumococcal vaccines.
• Conjugate vaccines: These vaccines are prepared by linking the polysaccharides or sugar molecules on the outer layer of the bacterium to a protein antigen or toxoid from the same or a different microbe. The polysaccharide coating disguises a bacterium`s antigens so that the immature immune systems of infants and younger children cannot recognize or respond to them. Conjugate vaccines get around this problem by enhancing the immunogenicity of the polysaccharides through the linkage with a protein. This formulation greatly increases the ability of the immune systems of young children to recognize the polysaccharide and develop immunity. Examples of conjugate vaccines include Haemophilus influenzae type B (Hib), pneumococcal and meningococcal vaccines.
• Toxoid vaccines: These vaccines are prepared from inactivated toxins, by treating the toxins with formalin, a solution of formaldehyde and sterilized water. This process of inactivation of toxins is known as detoxification and the resultant inactive toxin is known as a toxoid. Detoxification makes the toxins safe to use. The toxins used for the preparation of toxoids are obtained from the bacteria that secrete the illness-causing toxins. When the host body receives the harmless toxoid, the immune system adapts by learning how to fight off the natural bacterial toxin responsible for causing illness, by producing antibodies that lock onto and block the toxin. Examples of toxoid vaccines include diphtheria and tetanus toxoid vaccines.
• Recombinant protein vaccines: These vaccines are produced by using recombinant DNA technology, which involves inserting DNA encoding an antigen such as a bacterial surface protein into bacterial or mammalian cells, expressing the antigen in these cells, and then purifying it from them. Recombinant protein vaccines allow the avoidance of several potential concerns raised by vaccines based on purified macromolecules, such as contaminants or unwanted proteins. The production of recombinant protein vaccines also allows the production of sufficient quantities of purified antigenic components. Examples of recombinant protein vaccines include hepatitis B, human papillomavirus (HPV), influenza and coronavirus disease 2019 (COVID-19) vaccines.
• Nanoparticle vaccines: These vaccines are based on a strategy to present protein subunit antigens into the immune system using nanoparticles, which are microscopic particles that can self-assemble into various shapes and display antigens on their surface. Nanoparticle vaccines can stimulate a broad and long-term immune response and overcome some of the limitations of conventional subunit vaccines, such as stability and delivery issues. Nanoparticle-based experimental vaccines are being evaluated for influenza, respiratory syncytial virus (RSV), Epstein-Barr virus and malaria infections.

Subunit vaccines are generally safe for injection and have minimal side effects compared to whole-pathogen vaccines. The chances of adverse effects vary depending on the specific type of vaccine being administered. Minor side effects include injection site pain, fever, fatigue, headache and muscle ache, which usually resolve within hours or days after vaccination. Serious adverse effects consist of anaphylaxis and potentially fatal allergic reactions, but they are rare and occur in 1 to 1 million people who receive subunit vaccines. The contraindications for subunit vaccines are also vaccine-specific; they are generally not recommended for people with a previous history of anaphylaxis to any component of the vaccine. Advice from medical professionals should be sought before receiving any vaccination.

Nucleic acid vaccines are a novel type of vaccines that use the genetic material of the pathogen, either DNA or RNA, to induce an immune response in the host. Unlike conventional vaccines that introduce a weakened or killed pathogen or a subunit of it, nucleic acid vaccines deliver the instructions for the host cells to produce the antigen themselves. This way, the antigen is expressed in its native form and can elicit a strong and specific immune response.

There are two main types of nucleic acid vaccines: DNA vaccines and mRNA vaccines.

DNA vaccines

DNA vaccines consist of a circular piece of DNA called a plasmid that contains the gene encoding the antigen of interest. The plasmid also has a promoter sequence that allows the gene to be transcribed in the host cells. The plasmid is introduced into the host by various methods, such as injection, electroporation, gene gun, or microneedles. Once inside the cells, the plasmid is transported to the nucleus, where it is transcribed into mRNA. The mRNA then moves to the cytoplasm, where it is translated into the antigen protein by the ribosomes. The antigen protein is then presented on the cell surface by the major histocompatibility complex (MHC) molecules, where it can be recognized by the immune system.

DNA vaccines have several advantages over conventional vaccines, such as:

• They are easy and cheap to produce and store
• They are stable and do not require refrigeration or special handling
• They can induce both humoral and cellular immunity
• They can be designed to target multiple antigens or strains of a pathogen
• They have a low risk of contamination or reversion to virulence

However, DNA vaccines also have some limitations and challenges, such as:

• They may have low immunogenicity and require multiple doses or adjuvants
• They may induce immune tolerance or anergy if the antigen is expressed at low levels or for a long time
• They may cause unwanted integration into the host genome or trigger autoimmune reactions
• They may face regulatory and ethical hurdles for human use

Some examples of DNA vaccines that have been developed or tested for human diseases include:

• Hepatitis B: The first DNA vaccine approved for human use in 2005 by the Chinese FDA. It is marketed as Heberbiovac HB and has shown to be safe and effective in preventing hepatitis B infection.
• HIV: Several DNA vaccines have been tested in clinical trials for HIV prevention or treatment, but none have shown conclusive efficacy so far. Some of them include VRC-HIVDNA016-00-VP, PENNVAX-GP, and AGS-004.
• COVID-19: Several DNA vaccines are under development or testing for COVID-19 prevention, such as INO-4800, ZF2001, and AG0301-COVID19.

mRNA vaccines

mRNA vaccines consist of a synthetic messenger RNA (mRNA) molecule that encodes the antigen of interest. The mRNA is encapsulated in a lipid nanoparticle (LNP) that protects it from degradation and facilitates its delivery into the host cells. The LNP is injected into the host, where it fuses with the cell membrane and releases the mRNA into the cytoplasm. The mRNA is then translated into the antigen protein by the ribosomes. The antigen protein is then presented on the cell surface by the MHC molecules, where it can be recognized by the immune system.

mRNA vaccines have several advantages over conventional vaccines, such as:

• They are easy and fast to produce and modify
• They do not require any viral or bacterial vectors or culture systems
• They can induce both humoral and cellular immunity
• They do not integrate into the host genome or cause any genetic alteration
• They have a low risk of contamination or reversion to virulence

However, mRNA vaccines also have some limitations and challenges, such as:

• They are unstable and require ultra-cold storage and transportation
• They may have low immunogenicity and require multiple doses or adjuvants
• They may cause adverse reactions such as inflammation, fever, or allergic responses
• They may face regulatory and ethical hurdles for human use

Some examples of mRNA vaccines that have been developed or tested for human diseases include:

• COVID-19: The first mRNA vaccines approved for human use in 2020 by several regulatory agencies. They are marketed as Pfizer-BioNTech COVID-19 vaccine (BNT162b2) and Moderna COVID-19 vaccine (mRNA-1273) and have shown to be safe and effective in preventing COVID-19 infection.

• Influenza: Several mRNA vaccines are under development or testing for influenza prevention, such as BNT162b1, CV8102, and ARCT-021.

  Side effects of vaccines

Vaccines are generally safe and effective, but they can sometimes cause mild or moderate side effects that usually go away within a few days. These side effects are signs that the immune system is responding to the vaccine and building protection against the disease. However, in rare cases, some people may experience serious or severe side effects that require medical attention or emergency care.

Some of the common side effects of vaccines include:

• Pain, redness, swelling, or itching at the injection site
• Fever, chills, headache, fatigue, muscle or joint pain
• Nausea, vomiting, diarrhea, or abdominal pain
• Swollen lymph nodes
• Rash or hives

These side effects can be relieved by applying a cold compress to the injection site, drinking plenty of fluids, resting, and taking over-the-counter pain relievers or antihistamines as directed by a health care provider . However, it is not recommended to take these medicines before vaccination to prevent side effects, as it is not known how they might affect the vaccine`s effectiveness.

Some of the rare but serious side effects of vaccines include:

• Anaphylaxis: a severe allergic reaction that can cause difficulty breathing, swelling of the face and throat, a fast heartbeat, a rash all over the body, dizziness, and weakness . This can happen within minutes or hours of getting a vaccine and requires immediate medical care. People who have had an anaphylactic reaction to a vaccine or any of its ingredients should not receive that vaccine again.
• Thrombosis with thrombocytopenia syndrome (TTS): a blood clotting disorder that can cause serious problems such as stroke, heart attack, pulmonary embolism, or death. This can happen within three weeks of getting the Janssen/Johnson & Johnson COVID-19 vaccine and is more common in women under 50 years of age. People who have had TTS after getting this vaccine or any other adenovirus vector vaccine should not receive that vaccine again.
• Myocarditis and pericarditis: inflammation of the heart muscle or the lining around the heart that can cause chest pain, shortness of breath, or irregular heartbeat. This can happen within one week of getting an mRNA COVID-19 vaccine (Pfizer-BioNTech or Moderna), especially after the second dose and more often in males aged 12 to 29 years. Most cases are mild and resolve with rest and medication. People who have had myocarditis or pericarditis after getting an mRNA COVID-19 vaccine should avoid getting another dose of any COVID-19 vaccine.
• Guillain-Barre syndrome (GBS): a neurological disorder that can cause weakness, tingling, numbness, or paralysis of the limbs, face, or other parts of the body. This can happen within 42 days of getting the Janssen/Johnson & Johnson COVID-19 vaccine, mostly in men aged 50 to 64 years. Most cases recover with treatment but some may have long-term complications.

People who experience any of these serious side effects should seek immediate medical care and report them to their health care provider and to the Vaccine Adverse Event Reporting System (VAERS) in the U.S. or the Canada Vigilance Program in Canada . These systems help monitor the safety and effectiveness of vaccines and identify any potential problems.

It is important to remember that the benefits of vaccination outweigh the risks for most people. Vaccines can prevent serious and life-threatening diseases that can cause disability or death. By getting vaccinated, people can protect themselves and others from these diseases and help stop their spread. Vaccines are tested for safety and effectiveness before they are approved for use and are continuously monitored for any adverse events after they are administered. People who have questions or concerns about vaccines should talk to their health care provider or visit reliable sources of information such as:

• Centers for Disease Control and Prevention (CDC) - Vaccine Safety
• Food and Drug Administration (FDA) - Vaccine Safety
• Health Canada - Vaccine Safety
• Public Health Agency of Canada - Vaccine Safety

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