The development of vaccines and vaccine types is one of the most significant medical accomplishments which has helped to eradicate a large number of diseases. It has undergone an evolutionary process from live attenuated pathogen vaccine to killed whole organisms or inactivated toxins (toxoids), each of them having its advantages and disadvantages.
The crucial parameters in vaccination are the generation of memory response and protection against infection, while an important aspect is the effective delivery of antigen in an intelligent manner to evoke a robust immune response. In this regard, nanotechnology is greatly contributing to developing efficient vaccine adjuvants and delivery systems. These can protect the encapsulated antigen from the host’s in-vivo environment and release it in a sustained manner to induce a long-lasting immunostimulatory effect.
Infectious diseases that are caused by pathogens are one of the most important challenges faced by humans. In the past, diseases due to severe complications and high mortality have been horrific for people. Using vaccines in order to prevent and control diseases has been one of the greatest achievements in the history of medicine.
After the presentation of vaccines against infectious diseases, the world health organization (WHO) reported on the no-table decline in mortality and the complications of diseases, which are caused by vaccine types stability. Records signify the use of vaccine types in medical interventions, preventing the death of five persons per minute and 25 million deaths during the period between 2011 and 2020.
There are many advantages in the use of vaccines in comparison to common chemical drugs, such as longtime immunity, preventive and curative performance, and lack of drug resistance with the use of vaccines.
Vaccine types and Their Classification
In general, vaccines are divided into three generations based on the process of evolution and there are specific characteristics and covering spectrum in each generation.
First-Generation Vaccines
Attenuated and inactivated vaccines are identified in the first generation, which uses a primary method in their production. Attenuated pathogens, full organisms, or in-activated bacterial toxins, which are effectively immuno-genic, are used in making these vaccines.
There are some advantages in these kinds of vaccines due to their high ability to stimulate innate immunity, induction of long-term protection, easy production, and low production costs. However, there are some disadvantages in this generation, such as inducing disease due to the use of complete pathogen (live or inactivated) and virulence recursively of the pathogen in the host body. This type of vaccine is known as a traditional vaccine.
Attenuated Vaccine types
These kinds of vaccines, which are known as live attenuated vaccines, contain the major types of pathogens, which have all the pathogenic features of the main organisms and have been attenuated on laboratory conditions. These vaccines are useful as they have the ability to emulate the infection process, which could lead to the induction of potent antibody responses and cellular immunity. The advantages of attenuated vaccines include long-term safety and no need for a booster dose.
The procedures of attenuating an organism by pathogenic characteristics could be different. On the other hand, weak pathogenic trains like the type 2-poliovirus vaccine could also be used. In addition, the attenuation of pathogens could be obtainable by imposing strict conditions on pathogens. The triple vaccine of Measles, Mumps, and Rubella(MMR) is a kind of prominent attenuated vaccine, which was supplied in the United States in 1971. This vaccine contains all 3 types of viruses, which have been attenuated
Inactivated Vaccines types
In comparison with attenuated vaccines, the main advantage of inactivated vaccines is their usage of inactivated or killed pathogens, which cause an increase in safety and immunity level. However, there are some concerns, such as the return of the virulence characteristics of the pathogen, which leads to host disease, and because of non-proliferation, pathogens clear rapidly from the body, which could decrease the efficiency and effectiveness of vaccines in comparison with attenuated vaccines.
Hepatitis A is an inactivated vaccine that was produced by using the hepatitis A virus (type RG-SB), which is inactivated by formalin. The use of inactivated vaccines started in the early 1940s when Brazilian researchers have pioneered this field. Cutaneous Leishmaniasis vaccine is an inactivated vaccine, on which extensive studies have been done.
Second-Generation Vaccines
The first generation was made by live attenuated pathogens, which had the possibility of returning to natural and infectious forms and finally disease. Thus, to solve this problem, researchers and scientists offered second-generation vaccines.
The basis of this generation was subunit elements, recombinant or synthetic proteins, non-protein antigens, and expressed bacterial immunogens or viruses, which include numerous molecules and epitopes of different species and strains of pathogens. The subunit, conjugated, and recombinant vaccines are in this generation.
Subunit Vaccine types
Instead of the complete pathogen, parts are used for the production of these kinds of vaccines. Subunit vaccines have one or more protein peptides or polysaccharides, which are naturally found in the pathogenic structure. Due to the partial use of pathogens in subunit vaccines, they do not have the ability to pro-life rate and thereby make an unintended response. Because of their immunity and low production costs, they are viable alternatives to traditional vaccines. Bacterial subunit vaccines are divided into two basic types; the first type is Toxoid, in which toxins are the main pathogenic factor.
Toxins are inactivated by using inactive formaldehyde to change them to nontoxic forms (toxoid)and then they could be used for vaccination purposes. The close resemblance of toxoid and toxin enables the immune system to neutralize original toxins by antibodies. Tetanus, diphtheria, and pertussis toxoid vaccines could be considered in this category. This Cond type is made of a polysaccharide capsule of encapsulated bacteria. Because of the combination of antigen (usually bacterial polysaccharide) and the carrier protein, they are known as conjugates.
Conjugated Vaccine types
Polysaccharide antigens are large molecules with repetitive epitopes, and antigen-presenting cells are not enabled to process them, thus the antibody response occurs without the participation of T cells against them and causes a rise of antibody response at a small dose and short-time period. These responses were not able to make immune memory and affinity maturation for these kinds of infections. Unlike polysaccharide antigens, proteins could be processed well by antigen-presenting cells, and make long-term response and immunological memory.
In 1987, Hemophilus influenza B (HIB) was the first conjugate vaccine, which could obtain a license for medical usage and was later used for the immunization of infants. The Hib conjugate formulation made by different types of carrier proteins contains tetanus toxoid, diphtheria toxoid, diphtheria toxin mutant, and outer membrane protein, which caused increases in the quantity and quality of its immunogenicity.
The success of the conjugate vaccine in reducing the incidence of disease in children led to an acceleration of their development for preventing encapsulated pathogenic bacteria. The streptococcus pneumonia, meningococcal, and HIB belong to this group.
Recombinant Vaccines
Today, the rise of genetic engineering and molecular biology has had a great impact on the development and manufacturing process of vaccines. Specific antigenic microbes have high power to arouse the immune response against pathogens. Currently, the sequence of the pathogenic antigens could be obtainable by sequencing genes of the main antigen and producing them synthetically are-recombinant DNA technology.
Hepatitis B is the first and one of the most successful examples of synthetic vaccines. The surface antigen of this virus (HBsAg) is very immunogenic and effective, and able to produce high levels of antibody in the body. In the past, for providing hepatitis B vaccine, HBsAg was purified from the plasma of infection carriers and used for vaccination; of course, there were some extensive restrictions in purification, such as difficult conditions and contaminated plasma. In order to make recombinant hepatitis B vaccine, recombinant HBsAg is expressed in cells that have a powerful expression system (such as yeast) leading to the production of virus-like particles by HBsAgs, which are highly immunogenic. Since these particles have no genome, they do not create disease and lead to effective and powerful responses against the main pathogen. Other kinds of common vaccines are the anti-herpes simplex virus, anti-rotavirus, and anti-HPV vaccines.
Third-Generation Vaccines
Immunogenic potential administration of a plasmid containing a gene coding the antigen, known as genetic vaccines, is categorized as third-generation vaccines and is a valuable method, which has been considered by researchers since the beginning of the 1990s. Different names have been given for this kind of vaccines, such as DNA vaccines, RNA vaccines, and plasmid vaccines.
The expert committee of WHO vaccination in 1996 chose nucleotide acid that includes both DNA and RNA vaccines. Furthermore, genetic immunization and DNA immunization terms were used for this type of immunization. DNA vaccines include direct injection of a plasmid containing the encoding gene of the considered antigen, which is expressed in the cells with the aid of specific promoter that causes induction of the immune system. Therefore, instead of prescribing recombinant protein needed to stimulate the immune system (such as hepatitis B), it will be produced in the body.
The expressed protein, which is in the natural form, stimulates cellular and humeral immunity during different stages. The dendritic cells play an essential role in providing antigen to immune cells. The advantage of DNA vaccines are:
1)They do not have the limitation of common recombinant protein and peptide vaccines
2)Are able to immunize against several different strains of qualified antigen diversity
3) Produce antigen in a natural form and properly deliberated to the immune system
4) Are able to stimulate the humeral, cellular, and mucosal immunity
5)Can make sustainable immunity
6) Cause a lack of immune response to the injected vector and not generate antigen against transfected cells
7)There is no possibility to activate attenuated vaccines and infection risk
8) It has been possible to produce multiple vaccines
9) Have ease, speed of mass production and similar stages of vaccine production
10) The quality control is an easy process it is stable in various temperatures and the cold chain is not required for maintenance.
In addition to extensive benefits, DNA vaccines have some serious limitations, such as
1) The ability to be only used for protein antigens
2)Effect cells growth by controlling genes
3) Are capable of joining the host genome and inducing tumors
4) Can cause autoimmune diseases
In recent years, extensive research projects have been done on the use of this generation of vaccines for hepatitis, HIV, influenza, and Ebola. Nevertheless, they have not received indispensable licenses for human usage. Several clinical trials are ongoing on the use of these vaccines in cancers and human immunodeficiency virus (HIV). Some of the DNA vaccines obtain indispensable licenses in veterinary usage.
In the 21st century, expanding the new vaccine target population in age groups and specific human population was one of the most important aspects of vaccination.
In order to achieve such a goal, an increase of clinical trials on populations around the world and advanced technical facilities for the successful production of new vaccines were necessary. Today, there are some instructions for vaccine usage on different age groups and people with special conditions