Index
1- INTRODUCTORY CONCEPTS.
2- HOW ARE VACCINES MANUFACTURED?
3- WHAT IS A PLATFORM?
4- VACCINE PLATFORMS
- Live attenuated virus vaccines.
- Inactivated virus vaccines.
- Subunit, recombinant, polysaccharide and conjugate vaccines.
- Toxoid vaccines.
5- NEW VACCINE PLATFORMS
- Vaccines based on viral vectors.
- RNA- or DNA-based vaccines.
- Combined vaccines.
Introductory Concepts
The word immunity derives from the Latin adjective immunis, which means exemption from tasks and, from the biological point of view, refers to the action of protecting against infections.
Immunization consists of the induction and production of a specific protective immune response (antibodies and/or cell-mediated immunity) by a susceptible healthy individual as a consequence of the administration of a vaccine, which is an immunobiological product. The objective is to produce a response similar to that of natural infection, but without the dangers of suffering the disease and its consequences.
Artificial active immunization refers to the production of antibodies in response to the administration of a vaccine and natural active immunity is acquired when suffering the disease. Passive immunization involves the transfer of preformed antibodies, without mediating an immune response by the host. It is based on the administration of exogenously produced antibodies to the susceptible healthy individual in order to provide immediate protection, of limited duration, against the infectious agent to be protected. Like active immunity, passive immunity can be acquired naturally or artificially: natural immunity is acquired during pregnancy, through the placental passage of IgG, and during lactation, through colostrum. Artificial passive immunity is the transfer of already formed antibodies of the same or different species, the duration of which is approximately three months.
Individual immunity is the protection obtained by an individual when he/she receives vaccines that will protect him/her against the diseases to which they are directed. In contrast, the concept of herd, flock or collective immunity refers to the protection conferred by some vaccines to the entire population by preventing the transmission of the infectious agent. The diseases with which herd immunity can be generated are those that are transmitted from person to person, have a single host and provide specific and long-lasting immunity (examples are measles, polio, chickenpox, pneumococcus).
The term vaccine was coined by Edward Jenner, based on the name of the virus used to develop the antiviral vaccine. In 1798 he described that the inoculation of cowpox protected against human smallpox and that is where the name vaccine comes from: from the Latin vacca. He made this discovery some 60 years before the work of Pasteur and Koch formalized the microbial theory of disease.
Vaccines are among the great achievements of medicine. It is estimated that their use prevents between two and three million deaths per year and is considered one of the most cost-effective interventions that can be implemented in the population.
Adjuvants, from the Latin adjuvare (to help), are designed to improve the immunogenicity of vaccines. Examples of adjuvants are aluminum, alum or calcium compounds, ASO4, or MF59C.1 The adjuvant slows the absorption of the antigen by causing it to be exposed longer to the immune system. Immunobiologicals containing adjuvants must be injected deep into the muscle mass, as their inoculation into fat or intradermally can cause local irritation, granulomas or necrosis. Thus, adjuvants increase the immunogenicity of weak antigens, increase the speed and duration of the immune response, stimulate and modulate the humoral and cellular immune response, improve mucosal immunity and also help to reduce the dose of antigen required, thus reducing costs and, on occasions, the need for reinforcements.
Routes of administration of vaccines can be parenteral (subcutaneous, intramuscular injection), intradermal, intranasal or oral.
What is a platform?
A platform is the mechanism by which the immune system is presented with the infectious agent.
We can mention the following platforms as the most important ones:
- Live attenuated virus vaccines.
- Inactivated virus vaccines.
- Subunit, recombinant, polysaccharide and conjugate vaccines.
- Toxoid vaccines.
- New platforms including:
- Vaccines based on viral vectors.
- RNA- or DNA-based vaccines.
Vaccine platforms
Live attenuated virus vaccines
Live attenuated virus vaccines use viable viruses or bacteria that have been modified by successive passages under laboratory conditions or genetic manipulations. Because these new versions of the microbes are weakened, they cannot cause disease. They trigger robust cellular and humoral immune responses similar to natural infection and often provide long-term immunity. To produce an immune response, live vaccines must replicate in the vaccinated person, so they are contraindicated in immunosuppressed persons and pregnant women.
The immunity generated by these vaccines can be interfered by circulating antibodies from any source, whether transfusions, transplacental, and in these cases there can be failures in the response to the vaccine. One of their advantages is that they are generally effective with a single dose except when administered orally, e.g. OPV oral polio vaccine. In general, they do not require adjuvants.
These vaccines are fragile and can be damaged or destroyed by light or heat, so it is important to provide adequate handling and cold chain.
The live attenuated vaccines included in the national vaccination schedule are: live viral vaccines (measles, rubella, mumps, oral polio, yellow fever, Argentine hemorrhagic fever) and live bacterial vaccines (BCG).
Inactivated virus vaccines
Inactivated vaccines contain the entire microorganism or a portion of it killed or inactivated and this is achieved by different chemical (formalin, formaldehyde or propiolactone) or physical (heat or radiation) procedures.
In general, adjuvants and boosters are required to provide protective immunity and the immune response is less intense and long-lasting than in the case of the live virus and is fundamentally of a humoral type. In general, the first dose does not generate protective antibodies, it only alerts the immune system and protection develops only after the second or third dose. They tend to be more stable than live vaccines.
They are usually administered parenterally. Since these vaccines are not live, they cannot replicate and cannot cause disease, and can be received by immunocompromised and pregnant women. Vaccine response is not affected by the presence of circulating antibodies.
Examples of inactivated vaccines are: hepatitis A, injectable influenza vaccine, inactivated polio (Salk), rabies, whooping cough (whole cell) and COVID-19.
Comparative table between the most distinctive characteristics of these two types of vaccines:
Subunit, recombinant, polysaccharide and conjugate vaccines
These vaccines use germ-specific antigenic components produced by fractionation or biotechnology (proteins, sugar or capsid). As these vaccines use specific parts of the germ they provide an intense immune response that is directed against key sites of the microorganism. They require adjuvants and often boosters to provide protection against disease. They can be received by immunosuppressed patients and pregnant women.
The capsular polysaccharide of some microorganisms such as H. influenzae or pneumococcus are very poorly immunogenic in children under 2 years of age, so vaccines have been developed against the capsular polysaccharide called conjugates that have a protein as a transporter and trigger a robust response of T-facilitator or helper lymphocytes that are recognized by macrophages. This allows its use in children under 2 years of age, particularly in infants.
Examples of these vaccines: Haemophilus influenzae type b, hepatitis B, human papillomavirus, whooping cough (acellular), pneumococcal polysaccharide, meningococcal A/C,B/C, A/C/Y/W135, herpes zoster, respiratory syncytial virus, and COVID-19.
Toxoid vaccines
Vaccines with toxoids are obtained by chemical modification of the toxins produced by the germ against which we want to protect, thus preserving the antigenic power but without its pathogenicity. The immune system develops neutralizing antibodies against the toxin, instead of against the whole germ.
Like other types of vaccines, you may need boosters to provide protection. The main vaccines used with toxoids are diphtheria and tetanus.
New vaccine platforms
Vaccines based on viral vectors
They are produced by inserting genes for certain antigens of a pathogen into a non-pathogenic viral vector. This virus infects host cells and produces the immunogenic protein. Both a cell-mediated and a humoral immune response is generated and immunity against the viral vector may also develop.
Examples of these vaccines are those developed against surface protein (Spike) SARS-CoV-2 virus such as COVID-19 Vaccine, Ebola, HIV, Zika, Flu, etc.
RNA- or DNA-based vaccines
RNA-messenger and DNA vaccines are preparations in which the gene for a particular antigen is used, rather than the antigen itself which generates a protein that triggers the immune response against the virus.
The advantages of these types of vaccines are that they can be rapidly designed and manufactured and that large-scale production can be achieved in a short time. They often require multiple doses.
-DNA vaccines: are generated by inserting a gene encoding antigens into a bacterial-derived plasmid, which needs to be controlled by a promoter. They induce B and T type immune response.
-RNA vaccines There are two types, non-amplifying and self-amplifying. They contain 5 critical elements for life cycle and expression, require a lipid formulation and induce both cell-mediated and humoral immune responses. Examples of these vaccines are also those developed against SARS-CoV-2 virus.
Combination vaccines
It is the joint administration of several vaccines. It contains antigens of several infectious agents or different serotypes and/or serogroups of the same microbe, which are applied in a single administration. The combination can be made during manufacture, in the course of obtaining and preparation or at the time of administration. They can be of different antigens of the same microorganism (polyvalent vaccines) such as oral attenuated and inactivated parenteral polio vaccines, pentavalent rotavirus, HPV, pneumococcal polysaccharide or polysaccharide-conjugated vaccines against pneumococcus or meningococcus. They can also be combined vaccines with antigens of different microorganisms: viral vaccines such as MMR (measles, rubella and mumps) or bacterial vaccines such as DTaP / DPT / dT.
Authors: Scientific Advisory. Medical area. Science Team.
REFERENCES:
-Latin American Vaccine Manual. Edition 2021available at https://slipe.org/web/publicaciones/
-XVI Latin American Updating Course on Immunization at a distance 2023 - Ricardo Gutierrez Children's Hospital
- Pollard, Andrew J., and Else M. Bijker. "A guide to vaccinology: from basic principles to new developments." Nature Reviews Immunology 21.2 (2021): 83-100.
-American Academy of Pediatrics. Active and passive immunization. In: Kimberlin D, Brady M, Jackson M, et al., eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics;2018:13-64.
