Human Metapneumovirus (HMPV) is a common respiratory virus that circulates globally, often alongside other seasonal viruses like influenza and respiratory syncytial virus (RSV). Discovered in 2001, HMPV can cause a range of symptoms similar to the common cold, including cough, fever, and runny nose. While most infections are mild, HMPV can lead to more severe respiratory illnesses, particularly in vulnerable individuals. The global scientific community is actively working to develop a vaccine to prevent HMPV infections and reduce their associated health complications.
Understanding Human Metapneumovirus (HMPV)
HMPV is a virus that belongs to the Pneumoviridae family, which also includes RSV. It spreads primarily through respiratory droplets released from coughing and sneezing, close personal contact like touching or shaking hands, and by touching contaminated surfaces then touching the mouth, nose, or eyes. In temperate climates, HMPV activity typically peaks in late winter and spring, though it can circulate at lower levels year-round.
Common symptoms of HMPV infection include cough, fever, nasal congestion, runny nose, and shortness of breath. These symptoms often resemble those of other common respiratory viruses. However, HMPV can progress to more serious conditions such as bronchiolitis, an inflammation of the small airways, or pneumonia, an infection of the lungs. It can also worsen existing conditions like asthma or chronic obstructive pulmonary disease (COPD).
HMPV is a significant public health concern because it affects people of all ages, with most individuals experiencing an infection by age five. Infants, young children, older adults, and those with weakened immune systems face a higher risk of severe illness and hospitalization. For instance, studies indicate that HMPV infection rates and hospitalizations in certain populations can be comparable to those seen with RSV and influenza.
Approaches to HMPV Vaccine Development
HMPV vaccine development involves various strategies, each aiming to stimulate a protective immune response against the virus. One approach uses live-attenuated vaccines, weakened forms of the virus that can replicate without causing severe disease. These vaccines mimic natural infection, potentially eliciting a robust immune response involving both antibodies and T-cells. Some live-attenuated candidates have been genetically modified by removing certain viral proteins, such as G, SH, or M2-2, which are known to interfere with immune responses.
Another strategy involves subunit vaccines, which use specific viral proteins, typically the fusion (F) protein, to trigger an immune response. The F protein is a target because it is involved in viral entry into cells and is relatively conserved across HMPV strains. These vaccines can be administered as purified proteins or as virus-like particles (VLPs), structures resembling the virus but lacking genetic material, making them unable to replicate. VLPs displaying the F protein have shown promise in inducing neutralizing antibodies and T-cell responses in animal models.
mRNA vaccines represent a recent and rapidly developing platform, similar to those used for COVID-19. These vaccines deliver genetic instructions (mRNA) to cells, prompting them to produce the HMPV fusion protein. The immune system recognizes this protein and builds a defense against the actual virus. This technology allows for rapid design and manufacturing; combination mRNA vaccines targeting multiple respiratory viruses are also under investigation. Additionally, viral vector vaccines utilize a harmless virus to deliver HMPV genes into host cells, which express HMPV proteins to generate an immune response.
Current Status of HMPV Vaccines
Currently, no HMPV vaccine is licensed for public use, and there is no specific antiviral treatment for HMPV infection. Despite its discovery over two decades ago, developing a widely available HMPV vaccine has faced challenges, including the virus’s ability to evade immune responses and the need for long-lasting protection.
Some vaccine candidates are progressing through clinical trials. An investigational combination mRNA-based vaccine, mRNA-1653, is in development to prevent respiratory disease caused by both HMPV and Parainfluenza Virus Type 3 (PIV3). This bivalent vaccine contains two distinct mRNA sequences encoding the fusion proteins of HMPV and PIV3, encapsulated in lipid nanoparticles. A Phase 1 study of mRNA-1653 in healthy adults showed a single dose increased neutralizing antibody titers against both HMPV and PIV3.
Other clinical trials are evaluating mRNA-based investigational vaccines, such as mRNA-1345 and mRNA-1365, for protection against RSV and HMPV in infants and young children aged 5-23 months. These trials assess the safety and immune response of these candidates. Human challenge studies, where volunteers are intentionally infected with HMPV in a controlled environment, are being developed to accelerate vaccine and antiviral development. The final stage characterization study for an HMPV human challenge model is expected in the first half of 2025, with human challenge trials potentially commencing in the second half of the year.
Target Populations and Public Health Significance
A successful HMPV vaccine would benefit several populations, particularly those most susceptible to severe outcomes. Infants and young children are a primary target group, as HMPV commonly causes lower respiratory tract infections in this demographic, often leading to hospitalizations. Maternal vaccination, similar to strategies for other respiratory viruses, could offer protection to newborns and young infants through antibody transfer.
Older adults and individuals with compromised immune systems represent key populations that would benefit from an HMPV vaccine. These groups face increased risk of severe illness, including pneumonia and bronchiolitis, and can experience prolonged recovery periods. Vaccinating these vulnerable individuals could reduce their risk of severe disease, hospitalizations, and even mortality.
The broader public health impact of an HMPV vaccine would be significant. Widespread vaccination could reduce overall HMPV transmission, lessening the burden on healthcare systems by decreasing emergency room visits and hospital admissions. This would free up resources for other medical needs, particularly during peak respiratory virus seasons. A vaccine would contribute to improved global respiratory health, especially in areas with limited healthcare access, by preventing HMPV-related complications.