A Single Dose of an Avian H3N8 Influenza Virus Vaccine Is Highly Immunogenic and Efficacious against a Recently Emerged Seal Influenza Virus in Mice and Ferrets

Baz, Mariana; Paskel, Myeisha; Matsuoka, Yumiko; Zengel, James; Cheng, Xing; Treanor, John J.; Jin, Hong; Subbarao, Kanta

doi:10.1128/jvi.00280-15

Cited by 10 publications

(12 citation statements)

References 41 publications

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“…Recently, a live attenuated, cold-adapted H3N8 virus has been engineered using reverse genetics (31), and the results suggest that a single dose of this H3N8 vaccine induced a protective response in mice against homologous and heterologous viruses, including the Se H3N8 virus used in our study. Serological data from human and ferrets also suggest that this H3N8 vaccine may be protective.…”

Section: Discussionmentioning

confidence: 91%

Cross-Species Infectivity of H3N8 Influenza Virus in an Experimental Infection in Swine

Solórzano

Foni

Córdoba

et al. 2015

J Virol

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Avian influenza A viruses have gained increasing attention due to their ability to cross the species barrier and cause severe disease in humans and other mammal species as pigs. H3 and particularly H3N8 viruses, are highly adaptive since they are found in multiple avian and mammal hosts. H3N8 viruses have not been isolated yet from humans; however, a recent report showed that equine influenza A viruses (IAVs) can be isolated from pigs, although an established infection has not been observed thus far in this host. To gain insight into the possibility of H3N8 avian IAVs to cross the species barrier into pigs, in vitro experiments and an experimental infection in pigs with four H3N8 viruses from different origins (equine, canine, avian, and seal) were performed. As a positive control, an H3N2 swine influenza virus A was used. Although equine and canine viruses hardly replicated in the respiratory systems of pigs, avian and seal viruses replicated substantially and caused detectable lesions in inoculated pigs without previous adaptation. Interestingly, antibodies against hemagglutinin could not be detected after infection by hemagglutination inhibition (HAI) test with avian and seal viruses. This phenomenon was observed not only in pigs but also in mice immunized with the same virus strains. Our data indicated that H3N8 IAVs from wild aquatic birds have the potential to cross the species barrier and establish successful infections in pigs that might spread unnoticed using the HAI test as diagnostic tool. IMPORTANCEAlthough natural infection of humans with an avian H3N8 influenza A virus has not yet been reported, this influenza A virus subtype has already crossed the species barrier. Therefore, we have examined the potential of H3N8 from canine, equine, avian, and seal origin to productively infect pigs. Our results demonstrated that avian and seal viruses replicated substantially and caused detectable lesions in inoculated pigs without previous adaptation. Surprisingly, we could not detect specific antibodies against hemagglutinin in any H3N8-infected pigs. Therefore, special attention should be focused toward viruses of the H3N8 subtype since they could behave as stealth viruses in pigs.T he most ubiquitous hemagglutinin (HA) subtype of influenza A virus (IAV) is the H3, as it can be found in a variety of organisms, including humans, pigs, horses, dogs, cats, seals, poultry, and wild aquatic birds. Among all H3 subtypes, the H3N8 has turned out particularly interesting since it has established lineages not only in wild aquatic birds but also in mammalian species such as horses and dogs. At present, H3N8 is the only IAV subtype circulating in equine and canine species (1, 2). However, until now this subtype is not circulating in pigs and humans (1).Recently, equine H3N8 (clade II) strains have been isolated from pigs in China (3), but except for this publication no more data about transmission of equine IAV to pigs has been reported. Equine IAV has not been reported to cause disease in humans; however, a st...

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Section: Discussionmentioning

confidence: 91%

Cross-Species Infectivity of H3N8 Influenza Virus in an Experimental Infection in Swine

Solórzano

Foni

Córdoba

et al. 2015

J Virol

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“…Ferrets were weighed daily to monitor weight loss and nasal washes were collected on days 1, 3, 5, 7, and 9 post-challenge. Group size ( n = 4) was determined based on previous vaccine studies in ferrets 36 , 44 and the housing limitations within the BSL3 facility. Upon evaluation of ferret sera by microneutralization assay (Supplementary Table S4 ), one ferret in the mock-vaccinated group was found to have low levels of pre-existing antibody titers against H3N2 viruses.…”

Section: Methodsmentioning

confidence: 99%

Protective efficacy of influenza group 2 hemagglutinin stem-fragment immunogen vaccines

et al. 2017

Self Cite

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The stem of the influenza A virus hemagglutinin (HA) is highly conserved and represents an attractive target for a universal influenza vaccine. The 18 HA subtypes of influenza A are phylogenetically divided into two groups, and while protection with group 1 HA stem vaccines has been demonstrated in animal models, studies on group 2 stem vaccines are limited. Thus, we engineered group 2 HA stem-immunogen (SI) vaccines targeting the epitope for the broadly neutralizing monoclonal antibody CR9114 and evaluated vaccine efficacy in mice and ferrets. Immunization induced antibodies that bound to recombinant HA protein and viral particles, and competed with CR9114 for binding to the HA stem. Mice vaccinated with H3 and H7-SI were protected from lethal homologous challenge with X-79 (H3N2) or A/Anhui/1/2013 (H7N9), and displayed moderate heterologous protection. In ferrets, H7-SI vaccination did not significantly reduce weight loss or nasal wash titers after robust 107 TCID50 H7N9 virus challenge. Epitope mapping revealed ferrets developed lower titers of antibodies that bound a narrow range of HA stem epitopes compared to mice, and this likely explains the lower efficacy in ferrets. Collectively, these findings indicate that while group 2 SI vaccines show promise, their immunogenicity and efficacy are reduced in larger outbred species, and will have to be enhanced for successful translation to a universal vaccine.

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“…Virus antigen and RNA was found in bronchiolar epithelium by immunohistochemistry (IHC) and in situ-hybridization (ISH) [7,10]. Ferrets infected with this H3N8 virus demonstrated virus titers of above 10 6 TCID 50 /g in the nasal turbinates and the lungs [11]. The few pathological investigations on seals that died during this Seal/H10N7 outbreak report similar lesions, consisting of necro-suppurative bronchopneumonia with a bacterial co-infection [1,2].…”

Section: Introductionmentioning

confidence: 93%

“…In nine examined tracheal swabs (seal nos. [8][9][10][11][12][13][14][15][16] and in three examined nasal swabs (seal nos. 13-15) a positive signal was detected by the influenza A matrix gene real-time RT-PCR.…”

Section: Naturally Infected Harbor Seals With Seal/h10n7mentioning

confidence: 99%

Influenza A (H10N7) Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets

Brand¹,

Wohlsein²,

Herfst³

et al. 2016

PLoS ONE

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Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7) in harbor seals (Phoca vitulina). This epidemic caused high mortality in seals along the north-west coast of Europe and represented a potential risk for human health. To characterize the spectrum of lesions and to identify the target cells and viral distribution, findings in 16 harbor seals spontaneously infected with Seal/H10N7 are described. The seals had respiratory tract inflammation extending from the nasal cavity to bronchi associated with intralesional virus antigen in respiratory epithelial cells. Virus infection was restricted to the respiratory tract. The fatal outcome of the viral infection in seals was most likely caused by secondary bacterial infections. To investigate the pathogenic potential of H10N7 infection for humans, we inoculated the seal virus intratracheally into six ferrets and performed pathological and virological analyses at 3 and 7 days post inoculation. These experimentally inoculated ferrets displayed mild clinical signs, virus excretion from the pharynx and respiratory tract inflammation extending from bronchi to alveoli that was associated with virus antigen expression exclusively in the respiratory epithelium. Virus was isolated only from the respiratory tract. In conclusion, Seal/H10N7 infection in naturally infected harbor seals and experimentally infected ferrets shows that respiratory epithelial cells are the permissive cells for viral replication. Fatal outcome in seals was caused by secondary bacterial pneumonia similar to that in fatal human cases during influenza pandemics. Productive infection of ferrets indicates that seal/H10N7 may possess a zoonotic potential. This outbreak of LPAI from wild birds to seals demonstrates the risk of such occasions for mammals and thus humans.

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A Single Dose of an Avian H3N8 Influenza Virus Vaccine Is Highly Immunogenic and Efficacious against a Recently Emerged Seal Influenza Virus in Mice and Ferrets

Cited by 10 publications

References 41 publications

Cross-Species Infectivity of H3N8 Influenza Virus in an Experimental Infection in Swine

Cross-Species Infectivity of H3N8 Influenza Virus in an Experimental Infection in Swine

Protective efficacy of influenza group 2 hemagglutinin stem-fragment immunogen vaccines

Influenza A (H10N7) Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets

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