Trevor James
Parainfluenza viruses (PIVs) are single-stranded, negative-sense RNA viruses from the Paramyxoviridae family. They are a major cause of acute respiratory infections, especially in infants and young children. There are four distinct serological types, namely PIV-1, PIV-2, PIV-3, and PIV-4. While PIV-1 and PIV-2 are usually associated with croup, PIV-3 is more frequently linked to bronchiolitis and pneumonia. PIV-4, on the other hand, causes only mild upper respiratory infections and has not been associated with severe disease in young children. Currently, there is no approved vaccine for human parainfluenza viruses, and the development of effective vaccines is a significant area of focus.
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What You'll Learn
- Live attenuated vaccines for parainfluenza are being developed for intranasal delivery
- Parainfluenza vaccines aim to prevent acute lower respiratory illness (ALRI) in children
- There are four serotypes of parainfluenza viruses, PIV-1, PIV-2, PIV-3, and PIV-4
- Parainfluenza vaccines are also being developed for dogs
- Parainfluenza vaccines are distinct from influenza vaccines
Live attenuated vaccines for parainfluenza are being developed for intranasal delivery
Parainfluenza viruses are a group of viruses that cause acute lower respiratory illness (ALRI) worldwide. They are the second most common cause of ALRI, after human respiratory syncytial virus (RSV). Parainfluenza viruses are a major cause of hospitalization in young children, and they can also cause severe illness in the elderly and immunocompromised individuals. Currently, there is no approved vaccine for human parainfluenza virus type 3 (HPIV3), which is the most common and most pathogenic serotype. However, live attenuated vaccines for parainfluenza are being developed for intranasal delivery.
Live attenuated vaccines are a type of vaccine that uses a weakened version of the virus to stimulate an immune response and provide protection against the disease. These vaccines have the advantage of eliciting robust humoral and cellular immune responses that are predicted to be long-lived. For parainfluenza, live attenuated vaccines have been shown to be effective in animal studies and are expected to be more effective than inactivated vaccines.
The development of intranasal, live-attenuated HPIV3 vaccine candidates is underway, and these vaccines are designed to confer local mucosal and systemic immunity against infection. Codon-pair deoptimization (CPD) of HPIV3 open reading frames has resulted in vaccine candidates that show reduced replication in vivo while still stimulating a strong antibody response. These vaccine candidates have been shown to be immunogenic and protective in hamsters, and they are expected to provide protection against parainfluenza infection in humans as well.
Intranasal delivery of vaccines is a promising approach that can induce both local mucosal and systemic immunity. The nasal-associated lymphoid tissue is a mucosal inductive site for virus-specific humoral and cellular immune responses. In addition, intranasal administration of vaccines is non-invasive and convenient, making it a preferred method of delivery for many individuals.
Overall, the development of live attenuated vaccines for parainfluenza that can be delivered intranasally holds great promise for preventing and controlling this important respiratory virus. These vaccines have the potential to provide robust and long-lasting protection against parainfluenza infection, reducing the burden of disease, especially in young children and vulnerable populations.
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Parainfluenza vaccines aim to prevent acute lower respiratory illness (ALRI) in children
Parainfluenza viruses (HPIVs) are a common cause of acute upper and lower respiratory illness in infants, young children, the elderly, and the immunocompromised. HPIV3 is a significant pediatric respiratory pathogen that causes severe respiratory infections in young children worldwide. It is also the most common and pathogenic serotype of HPIVs, causing severe illness in the elderly and immunocompromised.
HPIVs are the second most common cause of acute lower respiratory illness (ALRI) in children under 5 years of age, resulting in approximately 1.6 million deaths annually. They are responsible for about 725,000 hospitalizations and 34,000 deaths among children under 5 years old worldwide each year. The overall pediatric HPIV disease burden is higher in low-income countries, which account for 70% of global in-hospital deaths due to HPIVs.
Currently, there are no approved vaccines or antiviral drugs for HPIV3. However, research is being conducted to develop vaccines against HPIV3 and other HPIVs. Efforts are being made to create a bivalent live vaccine that would provide protection against both influenza and parainfluenza virus infections. Reverse genetics systems (cDNAs) for HPIVs have helped identify attenuating mutations, and intranasal vaccines are being developed. HPIV3 vaccine candidates have shown promising results in hamsters, and HPIV1 and HPIV2 vaccines expressing RSV antigens could boost the immune response against RSV.
The development of effective vaccines against HPIVs is crucial to reducing the global burden of ALRI in children. Strategies such as codon-pair deoptimization (CPD) have been employed to create vaccine candidates that reduce replication in vivo while stimulating a protective antibody response. These advancements in vaccine development hold promise for preventing acute lower respiratory illness caused by HPIVs, particularly in vulnerable pediatric populations.
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There are four serotypes of parainfluenza viruses, PIV-1, PIV-2, PIV-3, and PIV-4
Parainfluenza viruses (PIVs) are single-stranded, enveloped RNA viruses belonging to the Paramyxovirus genus of the Paramyxoviridae family. There are four serotypes of human parainfluenza viruses: PIV-1, PIV-2, PIV-3, and PIV-4. These four serotypes are further defined by complement fixation and hemagglutinating antigens. PIV-1 and PIV-3 are members of the Respirovirus genus, while PIV-2 and PIV-4 belong to the Rubulavirus genus. Serotype 4 can be further subdivided into HPIV-4A and HPIV-4B.
PIVs are important human pathogens that can cause both upper and lower respiratory tract infections (URTI and LRTI) in children under five, adults, immunocompromised adults, and the elderly. They are one of the leading causes of morbidity and mortality in infants worldwide, particularly in low-income countries, which account for 70% of in-hospital deaths due to HPIVs. The overall pediatric HPIV burden is higher in these low-income countries.
PIV-1 and PIV-2 are the primary causes of croup (laryngotracheobronchitis), a viral disease of the upper airway that predominantly affects children aged 6 to 48 months. Biennial epidemics of croup typically begin in autumn and are associated with both PIV-1 and PIV-2, although PIV-2 can also cause yearly outbreaks. PIV-3 has been closely linked to bronchiolitis and pneumonia, mainly in children under one year of age. All four serotypes can be associated with pneumonia, but PIV-1 and PIV-3 are more commonly implicated.
Currently, there are no approved vaccines for human parainfluenza virus infections, although efforts are being made to develop effective vaccines. Inactivated vaccines for parainfluenza viruses have shown suboptimal protection and can even aggravate infection symptoms. On the other hand, live attenuated vaccines have proven effective in animal studies and are likely to be more promising for preventing both influenza and human parainfluenza virus infections.
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Parainfluenza vaccines are also being developed for dogs
Parainfluenza is a highly contagious ribonucleic acid virus that causes respiratory disease in dogs worldwide. It is a primary pathogen in canine infectious respiratory disease (CIRD), also known as kennel cough, which is spread by dogs in groups. While the singular impact of the canine parainfluenza virus (CPIV) is not severe, when it interacts with other pathogens, its impact becomes significant, especially in young or immunocompromised dogs.
Vaccines for CPIV have been developed and shown to be safe, with no clinical disease in vaccinated dogs and no traces of the vaccine virus in their blood or nasopharyngeal swabs. The vaccine produces neutralizing antibodies when administered either intramuscularly or subcutaneously, with intramuscular inoculation resulting in a significantly higher immune response. The vaccinated dogs also experienced a decreased respiratory shedding period of the challenge virus compared to seronegative control dogs.
Currently, combination intranasal and injectable vaccines for CPIV are recommended for dogs at risk for Bordetella bronchiseptica (Bb), as they have been shown to induce equivalent anamnestic (memory) Bb-specific IgG and IgA responses. The use of single-component oral and injectable Bb vaccines is not recommended, except for dogs that cannot be vaccinated intranasally or when used simultaneously with injectable core vaccines as a booster.
The duration of immunity for CPIV in household dogs is unknown, so it may be beneficial to use combination Bb and CPIV vaccines more frequently than annually, especially for high-risk patients. The strategy of combining different vaccines and routes of administration is called "heterologous prime-boost" and is being investigated to improve responses to vaccines, including for COVID-19.
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Parainfluenza vaccines are distinct from influenza vaccines
Parainfluenza and influenza are two distinct viruses that cause respiratory illnesses. While both can cause upper respiratory symptoms, they differ in severity and the specific symptoms they cause. Influenza typically causes more severe illness than parainfluenza, with symptoms such as high fever, body aches, and fatigue. On the other hand, parainfluenza often manifests as milder, cold-like symptoms, including a runny nose, cough, and low-grade fever. Importantly, influenza has effective vaccines available, whereas there are currently no vaccines specifically for parainfluenza viruses.
Influenza viruses belong to the Orthomyxoviridae family, whereas parainfluenza viruses (HPIVs) are part of the Paramyxoviridae family. This taxonomic distinction highlights the genetic differences between the two types of viruses. Influenza has a distinct seasonal pattern, with outbreaks primarily occurring during the winter months. In contrast, parainfluenza viruses circulate year-round, and each type has its own seasonal patterns.
The complications associated with influenza and parainfluenza also differ. Influenza is more likely to cause severe pneumonia in high-risk groups, while parainfluenza is more commonly associated with croup in children. Additionally, influenza can affect people of all ages, whereas parainfluenza predominantly affects young children, with most children being infected by the age of five.
The development of vaccines for influenza and parainfluenza has followed different paths. Influenza vaccines, such as inactivated influenza virus vaccines, are safe and effective in preventing influenza-related hospitalisations and deaths. However, the immune response triggered by these vaccines is often suboptimal and short-lived, requiring annual vaccination. On the other hand, there are currently no approved vaccines available for human parainfluenza viruses. While inactivated vaccines for parainfluenza have been studied in animals, they have been shown to aggravate the symptoms of infection upon challenge with the homologous virus.
While there is ongoing research to develop vaccines for parainfluenza, the focus has been on exploring alternative approaches. For example, live attenuated vaccines have shown promise in animal studies and are predicted to be more effective than inactivated vaccines for preventing both influenza and parainfluenza infections. Additionally, efforts have been made to create a bivalent live vaccine that could provide protection against both influenza and parainfluenza virus infections.
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