Microscopic view of Hepatitis A Virus with DNA sequence representing viral evolution.

Is Hepatitis A Under Control? The Viral Sequencing Revolution

Lena Voss in Health & Wellness December 2025 • 4 min read.

"How viral sequencing can revolutionize hepatitis A vaccination strategies and emergency response."

Hepatitis A virus (HAV) affects approximately 10 million people each year, remaining a significant global health concern despite the availability of an effective vaccine since 1995. Interest in HAV has waned over the last few decades, overshadowed by hepatitis B and C, yet its impact remains substantial.

HAV infection often goes unnoticed, particularly in children in high-incidence countries. This underestimation, coupled with limited research in developed countries with low incidence rates, necessitates further investigation into virus evolution and improved preventative measures, especially during outbreaks.

The multi-country HAV outbreaks in Europe between 2016 and 2017, predominantly affecting men who have sex with men (MSM), highlight the urgent need for enhanced control strategies in emergency situations. Viral sequencing is key to determining the virus mutations and strains that have spread.

Vaccine Shortages and the Importance of Tailored Vaccination Strategies

Microscopic view of Hepatitis A Virus with DNA sequence representing viral evolution.

The World Health Organization (WHO) recommends universal HAV vaccination, including two doses in national immunization schedules for children >1 year, based on incidence data and cost-effectiveness. However, some low-income countries and outbreak responses implement a single-dose regimen. Recent data suggests that single-dose regimens may result in a growing number of susceptible adults, as seen in the USA, where outbreaks persist due to lower hepatitis A immunization rates compared to other vaccines.

An EBioMedicine article by Sabria and colleagues supports this conclusion, presenting a deep-sequencing analysis of the complete capsid coding region of HAV from samples of the 2016-2017 Barcelona outbreak. Their study revealed amino acid replacements in and around the epitopes of vaccinated and non-vaccinated individuals, suggesting the emergence of vaccine-escape variants.

The Sabria article emphasizes the need to prevent the emergence of vaccine-escape variants, and raises questions regarding the efficacy of single-dose regimens during outbreaks:

A limited sample size.
The absence of information on neutralizing antibodies to HAV.
The inclusion of immunosuppressed (HIV-infected) patients, a condition that may impact the course of HAV infection.

The emergence of vaccine-escape mutations highlights the delicate balance between vaccine effectiveness and viral evolution. Continuous monitoring through viral sequencing is necessary to identify and respond to these emerging threats, ensuring that vaccination strategies remain effective.

Looking Ahead: Sequencing for Proactive Prevention

The global impact of HAV outbreaks is further evidenced by a 2016 outbreak in the Americas, particularly in Chile, primarily affecting MSM. Viral sequences from Chile were linked to the V16-25801 cluster, a predominant strain in Europe, suggesting potential intercontinental transmission.

These findings underscore the need for countries in epidemiological transition to rapidly distinguish between endemic outbreaks and those related to sexual transmission among MSM, as different control measures may be necessary. The study of vaccine-escape variants is critical in both endemic and non-endemic settings, given their potential to expand into the general population.

Novel sequencing strategies can reveal biological events during infections that appear under control. Understanding the co-evolution of HAV and the human host, leading to the selection of antigenic variants, offers new avenues for investigation. Enhanced monitoring, detailed guidelines for cases, and global scrutiny of vaccine-escape variants are essential for constructing predictive models of infection evolution and defining effective vaccination strategies.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.ebiom.2018.12.007, Alternate LINK

Title: Is Hepatitis A Virus Infection Under Control? Lessons In The Application Of Viral Sequencing For The Development Of Vaccination Schemes In Emergency Situations

Subject: General Biochemistry, Genetics and Molecular Biology

Journal: EBioMedicine

Publisher: Elsevier BV

Authors: Nora A. Fierro

Published: 2019-01-01

Everything You Need To Know

What is Hepatitis A?

Hepatitis A is a viral infection affecting approximately 10 million people annually. It is a significant global health concern despite the existence of an effective vaccine since 1995. The virus, known as HAV (Hepatitis A virus), can lead to outbreaks and, in some cases, is more prevalent in certain demographics such as men who have sex with men (MSM).

What is viral sequencing and why is it important in the context of Hepatitis A?

Viral sequencing is the process of analyzing the genetic material of viruses, like HAV. It's important because it helps in identifying virus mutations and strains. This is crucial for understanding how the virus evolves, tracking its spread during outbreaks, and assessing the effectiveness of vaccines. In the context of HAV, it allows for the detection of vaccine-escape variants, which can help tailor vaccination strategies.

What are vaccine-escape variants, and why are they a concern?

Vaccine-escape variants are mutations in the HAV that can potentially reduce the effectiveness of the vaccine. The Sabria article highlights the emergence of amino acid replacements in and around the epitopes, which are regions of the virus recognized by the immune system. These replacements can make it harder for the vaccine-induced antibodies to neutralize the virus, potentially leading to infections even in vaccinated individuals. Continuous monitoring through viral sequencing is essential to identify and address these variants.

What are the recommended HAV vaccination strategies, and why is tailoring them important?

The WHO (World Health Organization) recommends universal HAV vaccination, suggesting the importance of vaccination for children >1 year old, usually involving two doses in national immunization schedules. However, some low-income countries and in outbreak responses use a single-dose regimen. Recent data suggests that a single-dose regimen may result in a growing number of susceptible adults, which is a major concern. This is why tailoring vaccination strategies based on viral sequencing is important. This information can assist in establishing optimal vaccination strategies.

How does viral sequencing contribute to proactive prevention of Hepatitis A?

Viral sequencing has broader implications in proactive prevention. It allows for the tracking of virus transmission across different regions, as seen with the 2016 outbreak in the Americas. The sequencing identified the link between the Chilean outbreak and the V16-25801 cluster, a predominant strain in Europe, suggesting intercontinental transmission. This information helps in understanding the global spread of HAV, enabling more coordinated and effective control strategies.