How Can Vaccines Provide Immunity Against Antigenically Evolving Pathogens?

Article Summary:

Discussions on the evolution of pathogens and questions of vaccine efficacy are at an all-time high. Are vaccines effective in preventing severe illness if pathogens are capable of changing their genome to navigate through host defenses? This article explores viral antigen evolution. Vaccinations, while capable, have to go through more studies on improving efficacy among evolving pathogens. Alternate vaccine regimes should also be explored to understand their effectiveness.

With the current pandemic still underway and new antigenically persistent variants of the COVID-19 virus in the process of evolution, the efficacy of developing vaccines is a lingering question. While it may seem as though these viral mutations have the potential of causing catastrophic changes for new vaccine development, this isn’t so.

Many viral changes over the years, previously with the influenza virus and now with COVID-19, first appear to be significant but are minor when observing the overall picture. While such changes probably impact the severity or spread of viral pathogens, the other central aspects of the initial viral strain remain the same. This overall stability makes previous vaccine efficacy sufficient for new strains, with only minor tweaks potentially required.

The primary understanding of viral antigen evolution has been through the evolution of the influenza virus, for which seasonal vaccines are prepared annually.

Understanding Antigen Evolution Among Viruses

A primary reason for antigenic evolution is to evade the host’s immune response, enabling greater viral spread along with a more substantial disease impact. Epidemiologists have reported that viral antigen evolution has resulted in successive epidemics, especially when protective measures, efficient surveillance, and vaccines are not in place. The ongoing COVID-19 pandemic, especially during its early stages, was an example of this rapid antigen evolution.

What Are Antigenic “Drift” and “Shift”?

Antigenic drifts are the more frequent changes within viral genomes resulting in alteration of viral surface proteins; there are small changes in a few viral proteins, while the initial traits of the primary infecting virus are preserved. Drift changes occur within the host. However, over time, significant changes due to antigenic drift result in viral strains that are quite dissimilar from their original phylogenetic tree.

Antigenic drift is the cause of the evolving hemagglutinin (HA) and neuraminidase (NA) surface proteins of the influenza virus, which can result in decreased vaccine efficacy. It has resulted in the various flu pandemics of our past, the most recent being the H5N1 (avian flu).

However, in 2009, a novel H1N1 strain of the influenza virus seemed to originate within pigs. While there was an H1N1 outbreak in 1977, the viral strain during this 2009 epidemic seemed different, causing fatalities among young adults and children. A postulated reason for this catastrophe was a viral antigenic shift, and not drift.

As a result of antigenic shift, there is an abrupt change to the overall surface antigenic component of the influenza virus. An antigenic shift can occur when viral genomic strains combine and undergo reassortment. The resultant viral strain will be new within the current population. Therefore, even if there were previous exposure to a circulating influenza viral strain, there would be little immunity against a flu strain, or other viruses, produced through an antigenic shift.

Is Antigenic Evolution Only Present Among Viruses?

These changes in antigenic structures, which can lead to a completely different viral strain that is still a part of the same family, are observed mainly among viruses. For example, the influenza virus itself has four types, influenza A, B, C, and D. The most common one that leads to human infection and is the cause of outbreaks is influenza A. Influenza B is also known to infect humans but on a smaller scale.

When we look at bacteria in a similar light, the genomic evolution primarily results in changes in the bacterial structure and proteins. An example of such research looked for antigenic variation in gram-negative Neisseria. Changes in the outer membrane structure, the adhesins in the outer membrane, and the pilus of the bacteria were observed among evolved pathogens.

Similar changes can be noted among other bacteria, fungi, and parasites. In some cases, mutagenic properties within these pathogens can switch genes on or off based on host threats to their survival. However, these mutations often occur at an individual level to navigate host defenses and are rarely seen on the population scale observed with viral mutations.

How Are Vaccines Adapted for Evolving Pathogens?

Vaccines are the cornerstone for preventing and curbing severe threats from antigenically evolving strains of pathogens. Smallpox, polio, influenza, and even the current COVID-19 pandemic are a testament to this fact. Therefore, they must be effective against the current strains of each virus.

Why Are Seasonal Vaccines Necessary?

Millions of people globally develop the flu every year. The World Health Organization (WHO) estimated that approximately 650,000 deaths occur annually due to respiratory diseases caused by seasonal flu alone. The most significant mortality burden falls on the elderly, the very young, and those with comorbidities.

To lower the risk of severe illness and high mortality, developing strain-specific vaccines is paramount. Developing these seasonal vaccines also reduces the prevalence of flu infection over time. One theory postulates that consistent vaccine efficacy could also result in pathogen extinction through antigenic drift.

The seasonal flu vaccine only has an efficacy of about 40 to 60%. This suboptimal effectiveness is multifactorial, including age, comorbid conditions, and previous exposure to either another vaccine or influenza. In addition, a study has shown that certain even vaccine substrates can result in lower efficacy of a seasonal flu vaccine.

Despite all these factors, the benefits of receiving the seasonal flu vaccine, surpass any risks documented. It lowers both severities of disease and mortality rates due to influenza. Studies have highlighted a significant decline in ICU hospitalizations among those who receive the vaccine. Even among hospitalized patients, the number of days of hospital admission was lower among the vaccinated. This is especially useful for those who can suffer serious consequences from the flu such as the elderly or those with comorbidities such as COPD or diabetes.

Mosaic Vaccinations

The yearly seasonal vaccine’s sole purpose is to reduce severe illness from the evolving flu viral pathogen. Every year, researchers develop a vaccine against a new viral strain in hopes of robust action against it.

However, rapid pathogen evolution can curb these efforts, minimizing vaccines’ impact. While more effort can be channeled to develop more potent vaccines, a different strategy that is still being studied is mosaic vaccination. Under this vaccination strategy, every individual is vaccinated against a variety of viral strains with the hopes they will develop combined immunity against recent flu viral strains.

This strategy may be a futile attempt since variants differ and new variants may not have the antigenic targets of previous vaccines. However, a combination of doses could respond to antigenic evolution through the small changes observed through antigenic drift, especially during second or third waves of similar viral epidemics.

The Evolution of Antigens and the Future of Vaccinations

Pathogens will continue evolving in tandem with their hosts — often us — as they have been doing for millions of years and find ways to negate their host defenses and form more robust variants. For pathogens, robustness consists of their ability to spread from one host to the next, evade defenses, cause severe infection, and multiply within the host.

However, the human immune system is also inescapably in the process of continuous evolution, responding to the changes in pathogens’ tactics. Therefore, along with the advent of vaccinations, the impact of serious illness from any single pathogen has reduced significantly over time.

However, there are still concerns that require looking into and addressing with more robust vaccination strategies.

Can Vaccines Prevent Antigenic Escape?

Not only is the answer no, but it is fundamental to understand that the current vaccination system could actually speed up antigenic evolution and eventually lead to vaccine escape.

Due to pathogens evolving rapidly, they can escape host immune defenses and a vaccinated person can be infected with a different strain from the one targeted by the vaccine. Such escape has been primarily observed when more than one wave of a particular type of virus arises.

Another notable concern is that different strains can emerge from other geographical locations, as is currently being observed with the COVID-19 pandemic. Therefore, population immunity can differ from the current infecting strain, impacting vaccines’ development and long-term efficacy globally.

In such scenarios, exploring strategies such as mosaic vaccination, which could prevent possible waves from novel antigenic drift or provide immunization against re-emergent strains, should be considered.

Is Drug Resistance More of a Concern Over Vaccine Efficacy for Evolving Antigens?

Complete resistance by a pathogen to vaccinations is rare when considered in comparison to drug resistance.

Both drugs and vaccines assist the host immune capacity to tackle threats from infections. But simultaneously this builds pressure on the pathogen to evolve to escape host immune defenses.

Firstly, drug resistance is concerning, primarily when a drug is used directly against a pathogen. Rather than assisting the immune response, because the pathogen changes over time and the drug does not there is always a possibility that a strain emerges with resistance to the drug. Therefore, with time first-generation drugs become obsolete. This shows the need for research and development to create second and third-generation drugs. An example is the minimal use of first-generation penicillins and cephalosporins because antimicrobial resistance developed only a few years after the release of these drugs, negating their effectiveness. The quick onset of resistance required the rapid development of newer and stronger drugs.

Secondly, different antibiotic regimes are required for resistant bacterial strains during every infectious phase for patients with several comorbidities.

Thirdly, although drug resistance occurs primarily with bacteria, viruses such as influenza and herpes, for which drug regimens have long existed, have also encountered antiviral drug resistance.

When compared to vaccine efficacy, antigenic evolution is always on a smaller scale, resulting in smaller shifts within the pathogenic architecture. Viruses have been more effectively managed through vaccinations than through drug regimes. Moreover, vaccines boost the host’s immune response rather than tackling the pathogen directly. In which case, it can provide sustained immunity, with the requirement of regular booster shots. However, significant changes, such as observed with antigenic shifts, occur every few years, as seen with the 2009 flu epidemic. Nevertheless, vaccines against certain bacteria also have similar efficacy as those against viruses, which makes this a source of investigation in tackling antibiotic resistance concerns.

Conclusion

Antigenic evolution needs to be studied in a wider variety of pathogens to understand its intricacies. Additionally, with the ongoing pandemic, it is a great time to assess how vaccines developed for different strains can prove effective. Finally, health systems can also employ strategies such as mosaic vaccination while a vaccine’s development is in its infancy stages, such as for the current pandemic.

The evolution of COVID-19 is significantly different from that of influenza. Understanding these similarities and differences is vital in developing robust vaccination programs for future pathogenic attacks.

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