Does Mpox Vaccine Protect Against Smallpox

Mpox and smallpox, though caused by viruses in the same Orthopoxvirus genus, are distinct diseases. The question of whether the mpox vaccine protects against smallpox is a complex one, rooted in the virology of these diseases, the development and mechanism of action of the vaccines, and the historical context of smallpox eradication. Understanding the nuances of this relationship is crucial for public health preparedness and informed decision-making.

Understanding Mpox and Smallpox

Before delving into the efficacy of the mpox vaccine against smallpox, it is essential to understand the characteristics of each disease individually.

Mpox (formerly known as Monkeypox)

Mpox is a viral zoonotic disease, meaning it is transmitted from animals to humans. However, human-to-human transmission also occurs. The mpox virus causes symptoms similar to those seen in smallpox patients, although typically milder.

Symptoms:

• Fever
• Headache
• Muscle aches
• Swollen lymph nodes
• Rash that forms blisters and scabs

Transmission:

• Direct contact with the rash, scabs, or body fluids of an infected animal or person
• Respiratory droplets during prolonged face-to-face contact
• Contact with contaminated materials such as bedding

Severity:

While mpox is usually self-limiting, lasting two to four weeks, severe cases can occur, especially in individuals with weakened immune systems, children, and pregnant women. Complications may include secondary infections, pneumonia, encephalitis, and vision loss.

Smallpox

Smallpox was a highly contagious and often fatal disease caused by the Variola major virus. Thanks to a global vaccination campaign led by the World Health Organization (WHO), smallpox was eradicated in 1980. However, the threat of its re-emergence, whether through accidental release or intentional use as a bioweapon, remains a concern.

Symptoms:

• High fever
• Fatigue
• Severe back pain
• Rash that develops into characteristic raised, fluid-filled blisters that scab over

Transmission:

• Airborne droplets
• Direct contact with infected individuals or contaminated objects

Severity:

Smallpox was a devastating disease with a fatality rate of around 30%. Survivors often suffered permanent scarring, and blindness was a common complication.

The Science Behind Vaccines

To understand the cross-protective potential of the mpox vaccine, it is crucial to grasp the fundamental principles of vaccination and how vaccines induce immunity.

How Vaccines Work

Vaccines work by exposing the body to a weakened or inactive form of a pathogen (virus or bacteria) or a part of the pathogen (such as a protein). This exposure stimulates the immune system to produce antibodies and activate immune cells that can recognize and fight off the pathogen if encountered in the future. This creates immunological memory, providing protection against future infections.

Types of Vaccines Relevant to Mpox and Smallpox

• Live Attenuated Vaccines: These vaccines contain a weakened form of the live virus. They typically provide strong and long-lasting immunity but are not suitable for individuals with weakened immune systems. The original smallpox vaccine was a live attenuated vaccine.
• Non-Replicating Viral Vector Vaccines: These vaccines use a harmless virus (the vector) to deliver genetic material from the target pathogen into the body's cells. The cells then produce proteins that stimulate an immune response. The Modified Vaccinia Ankara (MVA) vaccine, used for mpox, is a non-replicating viral vector vaccine.
• Subunit Vaccines: These vaccines contain only specific parts of the pathogen, such as proteins, that are sufficient to trigger an immune response.

The Mpox Vaccine: A Closer Look

The mpox vaccines currently available are based on the vaccinia virus, which is closely related to both the mpox and smallpox viruses.

The Modified Vaccinia Ankara (MVA) Vaccine

The MVA vaccine is a live, attenuated vaccinia virus that has been modified to be safer than the original smallpox vaccine. It is replication-deficient in human cells, meaning it can enter cells and stimulate an immune response but cannot produce new infectious virus particles. This makes it safer for individuals with weakened immune systems.

Mechanism of Action:

The MVA vaccine works by introducing vaccinia virus antigens into the body. These antigens stimulate the immune system to produce antibodies and activate T cells that can recognize and fight off mpox and, potentially, smallpox.

Efficacy against Mpox:

Clinical trials have demonstrated that the MVA vaccine is highly effective in preventing mpox. Studies have shown that two doses of the MVA vaccine can provide significant protection against mpox infection and reduce the severity of the disease in those who do get infected.

Cross-Protection: Does the Mpox Vaccine Protect Against Smallpox?

The key question is whether the immune response generated by the mpox vaccine can provide cross-protection against smallpox.

Scientific Basis for Cross-Protection

The scientific basis for cross-protection lies in the fact that the mpox, smallpox, and vaccinia viruses share many similar antigens. When the body is exposed to the vaccinia virus in the mpox vaccine, it produces antibodies and T cells that can recognize and bind to these shared antigens. If the individual is later exposed to the smallpox virus, these pre-existing antibodies and T cells may be able to neutralize the virus and prevent infection or reduce the severity of the disease.

Historical Evidence

Historically, the original smallpox vaccine, which used a live vaccinia virus, was found to provide protection against mpox. This observation suggested that vaccination with vaccinia-based vaccines could offer cross-protection against different Orthopoxviruses.

Current Research and Evidence

While there is no definitive data on the efficacy of the current mpox vaccines against smallpox in humans (due to the eradication of smallpox), several lines of evidence suggest that the MVA vaccine can provide some level of protection:

• Animal Studies: Studies in animals have shown that vaccination with MVA can protect against challenge with the smallpox virus.
• Immunological Studies: Studies in humans have shown that the MVA vaccine induces antibodies and T cells that can recognize and neutralize the smallpox virus in vitro.
• Expert Opinion: Public health experts generally agree that the MVA vaccine is likely to provide some degree of protection against smallpox, although the level of protection may not be as high as that provided by the original smallpox vaccine.

Limitations and Considerations

It is important to note that the level of protection provided by the mpox vaccine against smallpox may be influenced by several factors:

• Vaccine Strain: The specific strain of vaccinia virus used in the vaccine can affect the level of cross-protection.
• Dosage and Timing: The number of doses of the vaccine and the timing of vaccination can also influence the level of protection.
• Individual Immune Response: The individual's immune response to the vaccine can vary, affecting the level of protection.
• Viral Load and Exposure Route: The amount of smallpox virus to which a person is exposed and the way they are exposed (e.g., airborne vs. direct contact) can also impact the effectiveness of the vaccine.

Public Health Implications

The potential for cross-protection between the mpox vaccine and smallpox has important implications for public health preparedness.

Stockpiling and Vaccination Strategies

Given the threat of smallpox re-emergence, many countries maintain stockpiles of the original smallpox vaccine. However, the MVA vaccine offers a safer alternative, particularly for individuals with weakened immune systems. Some public health agencies are considering using the MVA vaccine as a pre-emptive measure for certain populations at high risk of exposure to Orthopoxviruses.

Research and Development

Further research is needed to better understand the level of cross-protection provided by the MVA vaccine against smallpox. This research could involve:

• Developing better assays to measure the cross-neutralizing activity of antibodies induced by the MVA vaccine.
• Conducting clinical trials (if feasible and ethical) to assess the efficacy of the MVA vaccine against smallpox in humans.
• Developing new vaccines that offer even broader protection against Orthopoxviruses.

Conclusion

In summary, while the mpox vaccine is primarily designed to protect against mpox, there is a strong scientific basis to believe that it offers some degree of cross-protection against smallpox. The level of protection may not be complete, but it is likely to reduce the severity of the disease in those who are exposed to the smallpox virus. The mpox vaccine represents an important tool for public health preparedness and could play a crucial role in mitigating the impact of a potential smallpox outbreak. Continued research and strategic vaccination efforts are essential to ensure that we are adequately prepared for any future threats from Orthopoxviruses.