Live attenuated and inactivated vaccines

In this article, I briefly describe live attenuated and inactivated vaccines.

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Vaccines

A vaccine is a biological preparation that gives immunity to infectious diseases. The administration of vaccines is called vaccination. Edward Jenner was an English physician and scientist who pioneered the concept of vaccines including creating the smallpox vaccine, the world’s first vaccine. Vaccination is the most effective method of preventing infectious diseases.

Diseases like measles, mumps, diphtheria, pertussis (whooping cough), rubella (German measles), poliomyelitis, and tetanus have largely declined due to successful vaccination. Widespread immunity due to vaccination is largely responsible for the worldwide eradication of smallpox. Since October 1977, not a single naturally acquired smallpox case has been reported anywhere in the world. The worldwide restriction of the deadly Polio disease is another major achievement of vaccination.

When developing a vaccine, several key factors need to be considered. The vaccine must be both safe and effective in preventing infections. The approach should be feasible for the target population and also cost-efficient. Commonly used vaccines today include live but weakened organisms, inactivated (killed) bacterial cells or viruses, as well as protein or carbohydrate fragments (subunits) derived from the target pathogen.

Live attenuated vaccines

Attenuation is a process in which microorganisms lose their ability to cause significant disease. In other words, it reduces the pathogenicity of the microorganisms. By cultivating a pathogenic virus or bacterium under unusual culture conditions for an extended period, attenuation can be achieved. These attenuated microorganisms adapt to abnormal culture conditions, making them less likely to grow effectively in their natural host.

The BCG (Bacillus Calmette-Guerin) vaccine was developed by growing the pathogenic bacterium Mycobacterium bovis on a medium containing high concentrations of bile. After prolonged growth, the attenuated strain of M.bovis was suitable for the development of a vaccine for the highly infectious disease tuberculosis. The other attenuated vaccines developed are the measles vaccine, the Sabin polio vaccine, the mumps vaccine, the vaccine for chickenpox, and the vaccine for yellow fever disease. Finally, a new weakened form of Plasmodium falciparum is being used as a vaccine for malaria.

Advantages of attenuated vaccines

Attenuated vaccines are capable of transient growth, which stimulates a strong, effective, and long-lasting immune response. When compared to inactivated vaccines, attenuated vaccines produce a stronger and more durable immune response with a quick immunity onset. Attenuated vaccines encourage the body to create antibodies and memory immune cells in response to the specific pathogen. Thus, attenuated vaccines often require only a single immunization, eliminating the need for repeated boosters. Attenuated vaccines can replicate within host cells, for which they are suitable for inducing a cell-mediated response.

The oral polio vaccine (OPV) is an appropriate example of a live attenuated vaccine that has been in use for decades. Originally, it consisted of three attenuated strains of poliovirus. It is administered orally to children up to five years of age. The attenuated viruses colonize the intestine and induce the production of secretory IgA, which provides defense against naturally acquired poliovirus.

The vaccine also gives protective immunity to all three strains of virulent poliovirus by inducing IgM and IgG classes of antibodies. The oral polio vaccine needs boosters as the three strains of attenuated poliovirus can interfere with each other’s replication in the intestine. After the first immunization, one strain becomes dominant, triggering immunity to that specific strain. During the second immunization, the immunity developed from the initial dose suppresses the growth of the previously dominant strain, allowing one of the two remaining strains to establish itself in the intestines and stimulate immunity. By the third immunization, immunity to all three strains is generally achieved.

Disadvantages of attenuated vaccines

The attenuated vaccines have certain disadvantages as these live forms can mutate and revert to a more virulent form in the host. In the case of polio disease, the vaccinated individual has a risk of paralytic disease. The unprotected individuals who come in contact with these more virulent forms shed in feces and are also at risk of having paralytic disease. This reversion can allow pathogenic forms of the virus into the water supply and spread through a community where sanitation is not rigorous. However, the rate of reversion of the OPV to a virulent form is extremely low.

Attenuated vaccines may show complications like the natural disease. Some individuals after receiving the measles vaccine, develop some complications like postvaccination encephalitis. However, the vaccine-related complication is markedly lower than the risks from infection.

Methods of attenuating a virus

A virus can be attenuated irreversibly by applying genetic engineering. It can be done by selectively removing genes that are necessary for virulence or growth in the host. A herpes virus vaccine for pigs has been created by removing the thymidine kinase gene. Since this gene is essential for the virus to replicate in specific cell types, its removal made the virus non-pathogenic. Similarly, a live attenuated influenza vaccine, marketed as FluMist, was developed by cultivating the virus at lower-than-normal temperatures.

This process resulted in a cold-adapted strain that cannot replicate at the human body temperature of 37°C. This live attenuated virus can be administered intranasally which can cause a transient infection in the upper respiratory tract. This infection is enough to raise a strong immune response. The virus is unable to spread beyond the upper respiratory tract as it is unable to survive at the higher temperature of the inner body.

Inactivated vaccines

A pathogen can be killed by heat or chemical treatment and can be safely used in a vaccine. This makes the pathogen incapable of replication. However, the process allows the pathogen to induce an immune response to some of the antigens contained within the organism. During the process of inactivation, it is very important to maintain the structure of key epitopes on surface antigens. Among heat inactivation and chemical inactivation, the latter one has been more successful. Heat inactivation causes severe protein denaturation, thus any epitopes that depend on higher orders of protein structure can be significantly altered. The Salk-inactivated polio vaccine is produced by treating the poliovirus with formaldehyde treatment.

Inactivated vaccines, also called killed vaccines often require repeated boosters unlike the live attenuated vaccines, to achieve a protective immune status. Killed vaccines don’t replicate in the host, so they induce a humoral antibody response. These vaccines are less effective than the live attenuated vaccines in inducing cell-mediated immunity.

The risks associated with inactivated vaccines

If the inactivation procedure of killed vaccines is not properly carried out, then complications may arise. With the lack of proper inactivation procedures, the early Salk vaccines gave rise to serious complications as some of the viruses in two vaccine lots were not killed.

Handling large amounts of the infectious agent before inactivation poses a risk of infection to those involved. Nonetheless, inactivated vaccines are generally considered safer than live attenuated vaccines. They are widely used to protect against both viral and bacterial diseases.

Inactivated vaccines can be classified as whole virus vaccines, split virus vaccines, and subunit vaccines. Whole virus vaccines use the entire virus particle, fully destroyed using heat, chemicals, or radiation. Split virus vaccines are produced by using a detergent to disrupt the virus whereas subunit vaccines are produced by purifying out the antigens that best stimulate the immune system to mount a response to the virus.

Conclusion

Attenuation is a process in which microorganisms lose their ability to cause significant disease. By cultivating a pathogenic virus or bacterium under unusual culture conditions for an extended period, attenuation can be achieved. These attenuated microorganisms adapt to abnormal culture conditions, making them less likely to grow effectively in their natural host.

Attenuated vaccines are capable of transient growth, which stimulates a strong, effective, and long-lasting immune response. In comparison to inactivated vaccines, attenuated vaccines produce a stronger and more durable immune response with a quick immunity onset. Attenuated vaccines encourage the body to create antibodies and memory immune cells in response to the specific pathogen. The oral polio vaccine (OPV) is an appropriate example of a live attenuated vaccine that has been in use for decades. The attenuated vaccines have certain disadvantages as these live forms can mutate and revert to a more virulent form in the host.