Plaque Formation of Influenza Virus at 25° C

Hf, Maassab

doi:10.1038/219645a0

Cited by 38 publications

(20 citation statements)

References 3 publications

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“…The presence of ca and ts mutations in the internal gene segments of the AA/60 ca-based LAIV viruses permits efficient virus replication at 32 or 33°C but shuts off viral replication at 39°C (51,52). This restricts replication of the LAIV virus primarily to the upper respiratory tract, where temperatures are cooler, and this is believed to contribute to the attenuation of the vaccine virus in humans (15,51,53,54). The exact shutoff temperatures for the pLAIV viruses were not known, nor were differences in shutoff temperatures among influenza viruses of different subtypes or different origins.…”

Section: Resultsmentioning

confidence: 99%

The Matrix Gene Segment Destabilizes the Acid and Thermal Stability of the Hemagglutinin of Pandemic Live Attenuated Influenza Virus Vaccines

O’Donnell

Vogel

Matsuoka

et al. 2014

J Virol

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The threat of future influenza pandemics and their potential for rapid spread, morbidity, and mortality has led to the development of pandemic vaccines. We generated seven reassortant pandemic live attenuated influenza vaccines (pLAIVs) with the hemagglutinin (HA) and neuraminidase (NA) genes derived from animal influenza viruses on the backbone of the six internal protein gene segments of the temperature sensitive, cold-adapted (ca) A/Ann Arbor/60 (H2N2) virus (AA/60 ca) of the licensed seasonal LAIV. The pLAIV viruses were moderately to highly restricted in replication in seronegative adults; we sought to determine the biological basis for this restriction. Avian influenza viruses generally replicate at higher temperatures than human influenza viruses and, although they shared the same backbone, the pLAIV viruses had a lower shutoff temperature than seasonal LAIV viruses, suggesting that the HA and NA influence the degree of temperature sensitivity. The pH of HA activation of highly pathogenic avian influenza viruses was greater than human and low-pathogenicity avian influenza viruses, as reported by others. However, pLAIV viruses had a consistently higher pH of HA activation and reduced HA thermostability compared to the corresponding wild-type parental viruses. From studies with single-gene reassortant viruses bearing one gene segment from the AA/60 ca virus in recombinant H5N1 or pH1N1 viruses, we found that the lower HA thermal stability and increased pH of HA activation were associated with the AA/60 M gene. Together, the impaired HA acid and thermal stability and temperature sensitivity likely contributed to the restricted replication of the pLAIV viruses we observed in seronegative adults. IMPORTANCEThere is increasing evidence that the HA stability of influenza viruses depends on the virus strain and host species and that HA stability can influence replication, virulence, and transmission of influenza A viruses in different species. We investigated the HA stability of pandemic live attenuated influenza vaccine (pLAIV) viruses and observed that the pLAIV viruses consistently had a less stable HA than the corresponding wild-type influenza viruses. The reduced HA stability and temperature sensitivity of the pLAIV viruses may account for their restricted replication in clinical trials.

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Section: Resultsmentioning

confidence: 99%

The Matrix Gene Segment Destabilizes the Acid and Thermal Stability of the Hemagglutinin of Pandemic Live Attenuated Influenza Virus Vaccines

O’Donnell

Vogel

Matsuoka

et al. 2014

J Virol

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“…In mammals IAV is a respiratory pathogen that replicates in the cooler (33°C) upper respiratory tract, in addition to replicating in the warmer (37°C) conditions of the lower respiratory tract (31). This temperature difference has allowed for the development of cold-adapted (ca), temperature-sensitive (ts), attenuated (att) viruses that replicate in the upper respiratory tract but do not damage the lower respiratory tract due to the elevated temperatures restricting replication (32).…”

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confidence: 99%

Temperature-Sensitive Live-Attenuated Canine Influenza Virus H3N8 Vaccine

Nogales

Rodríguez

Chauché

et al. 2017

J Virol

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Canine influenza is a respiratory disease of dogs caused by canine influenza virus (CIV). CIV subtypes responsible for influenza in dogs include H3N8, which originated from the transfer of H3N8 equine influenza virus to dogs; and the H3N2 CIV, which is an avian-origin virus that adapted to infect dogs. Influenza infections are most effectively prevented through vaccination to reduce transmission and future infection. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV in dogs. However, the efficacy of IIVs is suboptimal, and novel approaches are necessary for the prevention of disease caused by this canine respiratory pathogen. Using reverse genetics techniques, we have developed a live-attenuated CIV vaccine (LACIV) for the prevention of H3N8 CIV. The H3N8 LACIV replicates efficiently in canine cells at 33°C but is impaired at temperatures of 37 to 39°C and was attenuated compared to wild-type H3N8 CIV in vivo and ex vivo. The LACIV was able to induce protection against H3N8 CIV challenge with a single intranasal inoculation in mice. Immunogenicity and protection efficacy were better than that observed with a commercial CIV H3N8 IIV but provided limited cross-reactive immunity and heterologous protection against H3N2 CIV. These results demonstrate the feasibility of implementing a LAIV approach for the prevention and control of H3N8 CIV in dogs and suggest the need for a new LAIV for the control of H3N2 CIV. IMPORTANCE Two influenza A virus subtypes has been reported in dogs in the last 16 years: the canine influenza viruses (CIV) H3N8 and H3N2 of equine and avian origins, respectively. To date, only inactivated influenza vaccines (IIVs) are available to prevent CIV infections. Here, we report the generation of a recombinant, temperature-sensitive H3N8 CIV as a live-attenuated influenza vaccine (LAIV), which was attenuated in mice and dog tracheal, explants compared to CIV H3N8 wild type. A single dose of H3N8 LACIV showed immunogenicity and protection against a homologous challenge that was better than that conferred with an H3N8 IIV, demonstrating the feasibility of implementing a LAIV approach for the improved control of H3N8 CIV infections in dogs.

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“…Forcing the virus to replicate efficiently at lower than normal temperatures resulted in changes to its genetic makeup making it less fit to replicate at normal and elevated body temperatures, thereby attenuating the strain. Biological characterization of ca A/Ann Arbor/6/60 and ca B/Ann Arbor/1/66 demonstrated that the resulting viruses are cold adapted, as defined by ability to replicate to titers at 25 C that were similar to titers obtained at 33 C. The strains are also temperature sensitive (ts), as defined by replication of the virus at 39 C that was debilitated compared to its replication at 33 C [14]. The spectrum of temperatures at which the ca virus replicated well was lower than the wild-type viruses that caused disease.…”

Section: Immunologymentioning

confidence: 98%

Live Attenuated Vaccines: Influenza, Rotavirus and Varicella Zoster Virus

Greenberg

Arvin

2010

Replicating Vaccines

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Since vaccinia virus was first used to protect against smallpox in the eighteenth century, live attenuated vaccines have proved to be highly effective in reducing the morbidity and mortality caused by many human viral pathogens. Contemporary live viral vaccines are designed using several different strategies to achieve attenuation. These basic principles and approaches are illustrated by vaccines to prevent rotavirus, influenza and varicella-zoster virus infections that are described in this chapter. As shown from the experience with these three vaccines, contemporary live attenuated viral vaccines have had a major impact on disease caused by these ubiquitous human pathogens.

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Plaque Formation of Influenza Virus at 25° C

Cited by 38 publications

References 3 publications

The Matrix Gene Segment Destabilizes the Acid and Thermal Stability of the Hemagglutinin of Pandemic Live Attenuated Influenza Virus Vaccines

The Matrix Gene Segment Destabilizes the Acid and Thermal Stability of the Hemagglutinin of Pandemic Live Attenuated Influenza Virus Vaccines

Temperature-Sensitive Live-Attenuated Canine Influenza Virus H3N8 Vaccine

Live Attenuated Vaccines: Influenza, Rotavirus and Varicella Zoster Virus

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