Types and Generation of Vaccines

Vaccines are the formulations (injections, liquids, pills, or nasal sprays) that deliver an immunogen, a non-harmful full Attenuated or inactivated or partial version of the virus or bacteria, to stimulate the immune system to recognize the pathogen when it is naturally encountered.

Through the administration of vaccines, the immune cells remain sensitized and ready to respond to the agent when it ever gains entry to the body.

This generates a slow to develop primary immune response, leading to the formation of a long-lasting memory cells.

When the real pathogen is encountered, the immune response is able to fight back more strongly and rapidly, protecting the individual from disease.

General mechanism of Immune Response generation:

When an antigen enters the body, it is recognized by immune cells and activates specific lymphocytes.

• In humoral immunity, the antigen activates B lymphocytes, which differentiate into plasma cells and produce specific antibodies that bind to and help eliminate the antigen.
• In cellular immunity, the antigen activates T lymphocytes, particularly helper and cytotoxic T cells; helper T cells coordinate the immune response, while cytotoxic T cells destroy infected or abnormal cells carrying the antigen.

Types and generations of Vaccines:

Vaccines can be classified in different ways based on the type of antigen used and the technology employed for their development. Broadly, vaccines are classified into conventional and modern vaccines. They can also be classified into first-, second-, and third-generation vaccines based on the development of vaccine technology

Whole organism Live-Attenuated Vaccines

Attenuated vaccines contain live but attenuated microorganisms that have lost most of their disease-causing ability but can still multiply temporarily in the host.

Attenuation is achieved by growing microorganisms under abnormal conditions for a prolong time. This process converts the microorganism’s habit to grow well under abnormal conditions but grow poorly in the natural host.

Due to this the attenuated species become less capable of causing disease but able to generate immune response.

Examples:

• BCG vaccine: Developed from Mycobacterium bovis by prolonged growth in a bile-containing medium for around 13 years.
• Sabin polio vaccine (OPV): Contains attenuated poliovirus. poliovirus used in the Sabin vaccine was attenuated by prolong growth in monkey kidney epithelial cells.
• Measles vaccine: Contains an attenuated measles virus that was grown for prolong time in duck embryo cells and later in human cell lines.
Advantage
• Produce a strong and long-lasting immune response.
• Stimulate the formation of memory cells.
• Usually require fewer doses and boosters.

Limitation
• The attenuated microorganism may revert to a disease-causing form in rare cases.

Inactivated Vaccines

Inactivated vaccines contain microorganisms that have been killed or inactivated by heat or chemicals, so they cannot multiply in the host.

Heat treatment is generally unsuitable because it can damage antigenic proteins structure, due to which the antigenic protein lost its ability to stimulate immune response. Therefore, chemicals such as formaldehyde and alkylating agents are often used.

Example: Salk polio vaccine (IPV), produced by inactivating poliovirus with formaldehyde.

Advantage

• Safe: They cannot cause infection because the microorganisms cannot multiply.
• Stable: They are generally more stable during storage than live attenuated vaccines.
• Suitable for many individuals: They do not carry the risk of reverting to a disease-causing form.

Limitation

• Weaker immune response: They generally produce a weaker immune response than live attenuated vaccines.
• Booster doses required: Multiple doses and booster vaccinations may be necessary to maintain immunity.
• Adjuvants may be needed: Additional substances may be required to improve the immune response.

Purified Macromolecules as Vaccines

Purified macromolecule vaccines contain specific components of microorganisms rather than whole microorganisms.

Three main types are inactivated toxins, capsular polysaccharides, and recombinant microbial antigens.

Capsular polysaccharide vaccines

Some bacteria have a polysaccharide capsule that protects them from phagocytosis by macrophages and neutrophils. These vaccines contain purified capsular polysaccharides that stimulate the production of antibodies. Sometime this capsular material is coated or attached with extra protein i.e. antibodies or adjuvants, that increases the antigenicity of the capsular material which further boost immune response.

Examples:

• Pneumococcal vaccine: Protects against Streptococcus pneumoniae, which can cause pneumonia. Some formulations contain polysaccharides from multiple bacterial types.
• Meningococcal vaccine: Protects against Neisseria meningitidis, which can cause bacterial meningitis.

Toxoid Vaccines

Some pathogenic bacteria, such as Corynebacterium diphtheriae and Clostridium tetani, produce poisonous substances called exotoxins, which cause the major symptoms of diphtheria and tetanus, respectively.

To prepare these vaccines, the exotoxins are purified and treated with formaldehyde to make them harmless. The inactivated toxins are called toxoids. Although toxoids cannot cause the harmful effects of the original toxins, they retain the ability to stimulate an immune response.

When a toxoid vaccine is administered, the body produces antibodies against the toxoid. These antibodies can also recognize and bind to the original toxin, neutralizing its harmful effects and protecting the body against disease.

Examples: Diphtheria toxoid vaccine and tetanus toxoid vaccine.

Recombinant Vaccines:

Recombinant vaccines are prepared using recombinant DNA technology, in which the gene responsible for producing an antigenic protein of a pathogen is introduced into a suitable host cell, such as bacteria, yeast, or mammalian cells. These cells produce the antigenic protein, which is then purified and used to prepare the vaccine.

Example: Hepatitis B Vaccine.

The hepatitis B vaccine is produced using recombinant DNA technology. The gene encoding the major surface antigen of the hepatitis B virus (HBsAg) is introduced into yeast cells. These genetically modified yeast cells are grown in large fermenters, where they produce HBsAg.

The yeast cells are then harvested and disrupted to release the antigen. The HBsAg is purified using suitable biochemical techniques and used to prepare the vaccine.

After vaccination, HBsAg stimulates the immune system to produce protective antibodies against hepatitis B virus, helping to prevent infection.

Synthetic Peptides as Vaccines

Synthetic peptide vaccines are prepared by chemically synthesizing short chains of amino acids (peptides) that represent specific antigenic regions of a pathogen.

Working principle:

1. First step is to identify a specific region of a pathogen's protein that can stimulate an immune response. This region is called an epitope.
2. The corresponding peptide is synthesized artificially in the laboratory.
3. The synthetic peptide is used as a vaccine, often with an adjuvant to improve the immune response.
4. The immune system recognizes the peptide and produces a specific immune response. This may help protect the body against the actual pathogen.

Advantages:

• They contain no live pathogens, so they cannot cause infection.
• They can be designed to target specific antigenic regions.
• They can be produced under controlled laboratory conditions.

Disadvantages:

• They may produce a weak immune response on their own.
• Adjuvants and booster doses may be required.
• Selecting peptides that produce strong and long-lasting protection can be difficult.

DNA Vaccines

DNA vaccines contain plasmid DNA carrying the gene that codes for a specific antigen of a pathogen. This DNA is introduced into the recipient's body, usually by injection into a muscle. After injection, some muscle cells and immune cells, such as dendritic cells, take up the plasmid DNA and produce the antigen encoded by it.

The immune system recognizes this antigen as foreign and produces an immune response.

DNA vaccines stimulate both types of immunity:

1. Humoral immunity: B cells produce antibodies against the antigen.
2. Cell-mediated immunity: T cells recognize and respond to the antigen, helping to protect the body against infection.

Advantages of DNA Vaccines;

• Natural antigen production: The antigen is produced inside the host cells in a form that generally resembles the natural protein produced by the pathogen.
• Both types of immunity: They stimulate both humoral and cell-mediated immune responses.
• No live pathogen required: They do not contain live microorganisms, so they cannot cause infection through replication of the vaccine organism.

Multivalent Subunit Vaccines

Multivalent subunit vaccines contain multiple antigenic components (epitopes) from a microorganism to stimulate an immune response against different parts of the pathogen.

One method of preparing these vaccines involves forming solid matrix–antibody–antigen (SMAA) complexes. In this method, monoclonal antibodies are attached to a solid particulate material. These antibodies then bind to specific antigens (proteins or peptides).

Different monoclonal antibodies can be attached to the same solid matrix to bind different antigens. In this way, multiple important epitopes recognized by B cells and T cells can be presented together in a single vaccine.

Mechanism of action: B-cell epitopes stimulate antibody production (humoral immunity), while T-cell epitopes activate T cells and promote cell-mediated immunity.

Advantages:

• Stimulate both humoral and cell-mediated immune responses.
• Present multiple epitopes in a single vaccine.
• May provide broader protection by targeting different antigenic regions of a pathogen.

ISCOMs and Liposomal vaccines

Immunostimulating complexes (ISCOMs) are special carriers used to deliver antigens and improve the immune response. They are prepared by combining proteins (antigens) with a detergent and a plant-derived glycoside called Quil A, which acts as an adjuvant and helps stimulate the immune system.

Liposomes are small, spherical vesicles made of lipid bilayers that can carry antigens. Both liposomes and ISCOMs can be used to deliver antigens derived from pathogens such as influenza virus, measles virus, hepatitis B virus, and HIV.

Mechanism of action: These carriers help deliver antigens into immune cells. The antigens can then be processed and presented to T cells, stimulating a cell-mediated immune response. They can also enhance antibody production, thereby improving the overall immune response.

Advantages:

• Improve the immunogenicity of antigens.
• Help deliver antigens into cells.
• Can stimulate both antibody-mediated and cell-mediated immune responses.

Conjugated Vaccines

Conjugated vaccines are vaccines in which a weak antigen, usually a bacterial capsular polysaccharide, is chemically linked to a carrier protein to produce a stronger immune response.

Mechanism of action:

1. The bacterial capsular polysaccharide alone produces a weak immune response, especially in infants.
2. It is linked to a carrier protein, such as a bacterial toxoid.
3. The protein helps activate helper T cells, which stimulate B cells to produce antibodies against the polysaccharide.
4. This produces a stronger, longer-lasting immune response and immunological memory.

Examples:

1. Haemophilus influenzae type b (Hib) vaccine: Hib capsular polysaccharide (polyribosylribitol phosphate, PRP) + carrier protein, such as tetanus toxoid or a meningococcal outer membrane protein.
. 2. Pneumococcal conjugate vaccine (PCV): Capsular polysaccharides from selected types of Streptococcus pneumoniae + a carrier protein, such as CRM197 (a non-toxic diphtheria toxin variant) or a tetanus-derived protein.
3. Meningococcal conjugate vaccine: Capsular polysaccharide of Neisseria meningitidis + a carrier protein, such as tetanus toxoid, diphtheria toxoid, or CRM197.