Vaccines prevent infectious diseases by preparing the immune system to combat specific pathogens. Scientists have developed various types of vaccines, each with a unique approach to generating immunity. This article explores a specific category known as live attenuated vaccines, examining how they are produced and how they interact with the immune system.
Understanding Attenuated Vaccines
An attenuated vaccine contains live viruses or bacteria that have been weakened in a laboratory. The term “attenuated” refers to this reduction in virulence, or the pathogen’s ability to cause disease, so the modified pathogen cannot produce significant illness in a healthy person. This approach differs from inactivated vaccines, which use pathogens that have been killed.
Because the weakened pathogens are still live, they can replicate within the body to a limited extent. This controlled, minor infection closely resembles a natural infection without causing the actual disease. This process allows the immune system to mount a comprehensive defense, leading to future immunity against the real pathogen.
Creating Weakened Pathogens: The Attenuation Process
Scientists use several techniques to reduce a pathogen’s virulence. One traditional method is serial passage, which involves repeatedly growing the pathogen in non-human host cells. For instance, a virus might be cultured in chicken embryos over many cycles. With each passage, the pathogen adapts to the foreign host and becomes less suited to replicating in human cells.
This adaptation results from evolutionary pressure, as the pathogen accumulates genetic mutations that favor survival in the new environment while diminishing its ability to cause disease in humans. For example, the measles vaccine was developed by passing the virus through chick embryo cells, while the varicella vaccine used guinea pig cells. After numerous passages, a strain is selected that is weak enough to be safe but still capable of inducing immunity.
A more modern approach is direct genetic modification. Using tools like CRISPR/Cas9, scientists can precisely edit the pathogen’s genetic code to remove or disable specific virulence genes. This method offers a high degree of control and predictability compared to serial passage. By targeting the molecular machinery the pathogen uses to cause illness, researchers can design a genetically stable and weakened version.
How Attenuated Vaccines Provoke Immunity
When the weakened pathogen is introduced into the body, it begins to replicate. Antigen-presenting cells (APCs) detect and process it, displaying fragments of the pathogen, known as antigens, on their surface. These APCs then travel to lymph nodes to alert other immune cells.
This alert activates the two primary arms of the adaptive immune system: humoral and cell-mediated immunity. Humoral immunity involves B-cells that mature and produce antibodies, which bind to the pathogen to neutralize it or mark it for destruction. Some B-cells become memory cells that persist for years and can rapidly produce antibodies upon future exposure.
Simultaneously, cell-mediated immunity is activated, involving T-cells. Cytotoxic T-lymphocytes, or killer T-cells, are trained to identify and destroy body cells infected by the vaccine virus. The combination of antibody production and cell-mediated killing creates a durable immunological memory, often providing long-lasting protection with just one or two doses.
Examples of Attenuated Vaccines in Use
Several widely administered vaccines use the attenuated pathogen approach to control infectious diseases.
- The measles, mumps, and rubella (MMR) vaccine combines three live attenuated viruses to protect against these common childhood illnesses.
- The varicella vaccine contains a weakened form of the varicella-zoster virus to prevent chickenpox.
- The rotavirus vaccine is administered orally to prevent severe diarrhea and dehydration in infants by providing localized immunity in the gut.
- The yellow fever vaccine contains an attenuated virus to prevent a mosquito-borne disease found in parts of Africa and South America.
- Historically, the oral polio vaccine (OPV) was an attenuated vaccine that played a large role in the global effort to eradicate polio.
- The intranasal influenza vaccine (FluMist) delivers a weakened flu virus directly to the nasal passages to stimulate an immune response at the site of entry for the natural virus.
Important Considerations for Attenuated Vaccines
The live nature of attenuated vaccines necessitates certain precautions. Because the weakened pathogens replicate in the body, these vaccines are not recommended for individuals with compromised immune systems. This includes people with HIV/AIDS, patients undergoing chemotherapy, or those taking immunosuppressive drugs. In these individuals, the pathogen could replicate without control and cause a serious infection.
For similar reasons, live attenuated vaccines are contraindicated for pregnant women. This is a precautionary measure to avoid any theoretical risk of the vaccine virus crossing the placenta and affecting the developing fetus.
Some recipients of attenuated vaccines may experience mild symptoms that resemble a less severe version of the natural disease, such as a low-grade fever or a faint rash after the MMR vaccine. This occurs as the weakened virus replicates and is a sign that the immune system is responding to the vaccine. There is also an extremely rare possibility that a vaccine virus could revert to a more virulent form through genetic mutation. Modern manufacturing and testing standards are designed to minimize this risk, making such events uncommon.