Live recombinant vaccines are biological preparations that stimulate immune responses to a pathogen through the use of genetically modified live bacteria or viruses. These live pathogens are biologically engineered to express exogenous antigens in the cytoplasm of target cells, thereby triggering immune responses. [1] This form of vaccine combines the beneficial features of attenuated and recombinant vaccines, providing the long-lasting immunity of attenuated vaccines’ with recombinant vaccines’ genetically engineered precision and safety. [2]
Live recombinant vaccines can be administered via orally or nasally, instead of injection. Common examples of vaccines with the aforementioned route of admission include the oral polio vaccine and the nasal spray influenza vaccine. [3] [4] These vaccines can stimulate mucosal immunity and eliminate adverse effects associated with injection. [5] Research and development efforts focus on enhancing live recombinant vaccines to offer heightened protection and broader coverage against various bacteria and virus serotypes. [6]
The first vaccine was for smallpox. Edward Jenner used cowpox pus to create immunity. [7] Notable subsequent vaccines include polio, flu (influenza), hepatitis A and B, measles, rotavirus, and pneumococcal disease. [8]
Live vaccines include live attenuated (MMR-II), rVSV-ZEBOV vaccine (Ebola), and live recombinant vaccines. [9]
Using a mechanism similar to infections that occur naturally, live recombinant vaccines can generate immunity that is robust and long-lasting. [2] Pathogens in traditional live attenuated vaccines can cause disease in hosts with immune-compromised, damaged or weakened immune systems. Live recombinant vaccines are genetically engineered to inhibit their disease-causing ability. This reduces the chances of infection after vaccination. [10] [11] There are currently no widely deployed live recombinant vaccines.
Recombinant vaccines causing protein, viral vectors and conjugates are under research. [12] Research is searching for better Streptococcus vaccines. Existing polyvalent vaccines protect against as many as 23 serotypes, but need to address the entire set of 100 serotypes. [13] In 2021, 2 vaccines were launched by Pfizer and Merck: Prevnar 20 (PCV-20) and Vaxneuvance (PCV-15), respectively. [14] Vaxneuvance covers 5 fewer serotypes, but the combination of Pneumovax 23 with Vaxneuvance covers more serotypes than Prevnar20. [15] Vaccines are heading for stronger protection against known serotypes, but also attack other strains or serotypes. [6]
While live recombinant vaccines are generally considered to be safe, genetically modified organisms can potentially revert to pathogenic modes, causing disease, particularly in young, immunocompromised and/or older subjects. [16]
Poliomyelitis, commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 75% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe symptoms develop such as headache, neck stiffness, and paresthesia. These symptoms usually pass within one or two weeks. A less common symptom is permanent paralysis, and possible death in extreme cases. Years after recovery, post-polio syndrome may occur, with a slow development of muscle weakness similar to what the person had during the initial infection.
A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and recognize further and destroy any of the microorganisms associated with that agent that it may encounter in the future.
Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all children be fully vaccinated against polio. The two vaccines have eliminated polio from most of the world, and reduced the number of cases reported each year from an estimated 350,000 in 1988 to 33 in 2018.
Poliovirus, the causative agent of polio, is a serotype of the species Enterovirus C, in the family of Picornaviridae. There are three poliovirus serotypes, numbered 1, 2, and 3.
Enterovirus is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine.
Contact immunity is the property of some vaccines, where a vaccinated individual can confer immunity upon unimmunized individuals through contact with bodily fluids or excrement. In other words, if person "A" has been vaccinated for virus X and person "B" has not, person "B" can receive immunity to virus X just by coming into contact with person "A". The term was coined by Romanian physician Ioan Cantacuzino.
Artificial induction of immunity is immunization achieved by human efforts in preventive healthcare, as opposed to natural immunity as produced by organisms' immune systems. It makes people immune to specific diseases by means other than waiting for them to catch the disease. The purpose is to reduce the risk of death and suffering, that is, the disease burden, even when eradication of the disease is not possible. Vaccination is the chief type of such immunization, greatly reducing the burden of vaccine-preventable diseases.
Pneumococcal conjugate vaccine is a pneumococcal vaccine made with the conjugate vaccine method and used to protect infants, young children, and adults against disease caused by the bacterium Streptococcus pneumoniae (pneumococcus). It contains purified capsular polysaccharide of pneumococcal serotypes conjugated to a carrier protein to improve antibody response compared to the pneumococcal polysaccharide vaccine. The World Health Organization (WHO) recommends the use of the conjugate vaccine in routine immunizations given to children.
A breakthrough infection is a case of illness in which a vaccinated individual becomes infected with the illness, because the vaccine has failed to provide complete immunity against the pathogen. Breakthrough infections have been identified in individuals immunized against a variety of diseases including mumps, varicella (Chickenpox), influenza, and COVID-19. The characteristics of the breakthrough infection are dependent on the virus itself. Often, infection of the vaccinated individual results in milder symptoms and shorter duration than if the infection were contracted naturally.
Pneumococcal vaccines are vaccines against the bacterium Streptococcus pneumoniae. Their use can prevent some cases of pneumonia, meningitis, and sepsis. There are two types of pneumococcal vaccines: conjugate vaccines and polysaccharide vaccines. They are given by injection either into a muscle or just under the skin.
An attenuated vaccine is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable. Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent. These vaccines contrast to those produced by "killing" the pathogen.
The rabies vaccine is a vaccine used to prevent rabies. There are several rabies vaccines available that are both safe and effective. Vaccinations must be administered prior to rabies virus exposure or within the latent period after exposure to prevent the disease. Transmission of rabies virus to humans typically occurs through a bite or scratch from an infectious animal, but exposure can occur through indirect contact with the saliva from an infectious individual.
An adenovirus vaccine is a vaccine against adenovirus infection. According to American CDC, "There is currently no adenovirus vaccine available to the general public.
A subunit vaccine is a vaccine that contains purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response. Subunit vaccine can be made from dissembled viral particles in cell culture or recombinant DNA expression, in which case it is a recombinant subunit vaccine.
An inactivated vaccine is a type of vaccine that contains pathogens that have been killed or rendered inactive, so they cannot replicate or cause disease. In contrast, live vaccines use pathogens that are still alive. Pathogens for inactivated vaccines are grown under controlled conditions and are killed as a means to reduce infectivity and thus prevent infection from the vaccine.
Vaccine shedding is a form of viral shedding which can occasionally occur following a viral infection caused by an attenuated vaccine. Illness in others resulting from transmission through this type of viral shedding is rare. The idea of shedding is a popular anti-vaccination myth. However, most vaccines are not attenuated vaccines, and therefore cannot cause vaccine-induced viral shedding.
A vaccine dose contains many ingredients very little of which is the active ingredient, the immunogen. A single dose may have merely nanograms of virus particles, or micrograms of bacterial polysaccharides. A vaccine injection, oral drops or nasal spray is mostly water. Other ingredients are added to boost the immune response, to ensure safety or help with storage, and a tiny amount of material is left-over from the manufacturing process. Very rarely, these materials can cause an allergic reaction in people who are very sensitive to them.
A viral vector vaccine is a vaccine that uses a viral vector to deliver genetic material (DNA) that can be transcribed by the recipient's host cells as mRNA coding for a desired protein, or antigen, to elicit an immune response. As of April 2021, six viral vector vaccines, four COVID-19 vaccines and two Ebola vaccines, have been authorized for use in humans.
Vaccine resistance is the evolutionary adaptation of pathogens to infect and spread through vaccinated individuals, analogous to antimicrobial resistance. It concerns both human and animal vaccines. Although the emergence of a number of vaccine resistant pathogens has been well documented, this phenomenon is nevertheless much more rare and less of a concern than antimicrobial resistance.
A genetic vaccine is a vaccine that contains nucleic acids such as DNA or RNA that lead to protein biosynthesis of antigens within a cell. Genetic vaccines thus include DNA vaccines, RNA vaccines and viral vector vaccines.