scholarly journals Neuraminidase in Virus-Like Particles Contributes to the Protection against High Dose of Avian Influenza Virus Challenge Infection

Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1291
Author(s):  
Hae-Ji Kang ◽  
Ki-Back Chu ◽  
Keon-Woong Yoon ◽  
Gi-Deok Eom ◽  
Jie Mao ◽  
...  

Neuraminidase is an important target for influenza vaccination. In this study, we generated avian influenza VLPs, expressing hemagglutinin (HA), neuraminidase (NA), HA and NA co-expressed (HANA), to evaluate the protective role of NA against a high (10LD50) and low (2LD50) dose of avian influenza virus challenge infections. A single immunization with HANA VLPs elicited the highest level of virus-specific IgG, IgG1, and IgG2a responses from the sera post-vaccination and the lungs post-challenge-infection. Potent antibody-secreting cell responses were observed from the spleens and lungs of HANA-VLP-immunized mice post-challenge-infection. HANA VLPs induced the highest CD4+ T cell, CD8+ T cell, and germinal center B cells, while strongly limiting inflammatory cytokine production in the lungs compared to other VLP immunization groups. In correlation with these findings, the lowest bodyweight losses and lung virus titers were observed from HANA VLP immunization, and all of the immunized mice survived irrespective of the challenge dose. Contrastingly, VLPs expressing either HA or NA alone failed to elicit complete protection. These results indicated that NA in VLPs played a critical role in inducing protection against a high dose of the challenge infection.

2008 ◽  
Vol 89 (4) ◽  
pp. 968-974 ◽  
Author(s):  
Thomas W. Vahlenkamp ◽  
Timm C. Harder ◽  
Matthias Giese ◽  
Fengsheng Lin ◽  
Jens P. Teifke ◽  
...  

Highly pathogenic avian influenza virus (HPAIV) H5N1 of Asian origin continues to circulate in poultry and wild birds, causing considerable concern for veterinary and public health in Asia, Europe and Africa. Natural transmission of HPAIV H5N1 from poultry to humans, resulting in infections associated with high mortality, and from poultry or wild birds to large felids and domestic cats has been reported. Experimental infection of cats with HPAIV H5N1 derived from a human patient resulted in lethal disease. The role of cats in the adaptation of HPAIV H5N1 to mammals and vaccination regimens for the eventual protection of cats, however, remain to be elucidated. Here, it was shown that cats can be protected against a lethal high-dose challenge infection by an inactivated, adjuvanted heterologous H5N6 avian influenza virus vaccine. The challenge HPAIV H5N1 was derived from a naturally infected cat. In non-vaccinated cats, low-dose exposure resulted in asymptomatic infections with minimal virus excretion. As diseased cats can transmit the infection to naïve contact animals, the epidemiological role of H5N1-infected cats in endemically infected areas as a link between wild birds, poultry and humans needs close inspection, and vaccination of cats should be considered to reduce possible human exposure.


2006 ◽  
Vol 80 (4) ◽  
pp. 1959-1964 ◽  
Author(s):  
Wentao Gao ◽  
Adam C. Soloff ◽  
Xiuhua Lu ◽  
Angela Montecalvo ◽  
Doan C. Nguyen ◽  
...  

ABSTRACT The recent emergence of highly pathogenic avian influenza virus (HPAI) strains in poultry and their subsequent transmission to humans in Southeast Asia have raised concerns about the potential pandemic spread of lethal disease. In this paper we describe the development and testing of an adenovirus-based influenza A virus vaccine directed against the hemagglutinin (HA) protein of the A/Vietnam/1203/2004 (H5N1) (VN/1203/04) strain isolated during the lethal human outbreak in Vietnam from 2003 to 2005. We expressed different portions of HA from a recombinant replication-incompetent adenoviral vector, achieving vaccine production within 36 days of acquiring the virus sequence. BALB/c mice were immunized with a prime-boost vaccine and exposed to a lethal intranasal dose of VN/1203/04 H5N1 virus 70 days later. Vaccination induced both HA-specific antibodies and cellular immunity likely to provide heterotypic immunity. Mice vaccinated with full-length HA were fully protected from challenge with VN/1203/04. We next evaluated the efficacy of adenovirus-based vaccination in domestic chickens, given the critical role of fowl species in the spread of HPAI worldwide. A single subcutaneous immunization completely protected chickens from an intranasal challenge 21 days later with VN/1203/04, which proved lethal to all control-vaccinated chickens within 2 days. These data indicate that the rapid production and subsequent administration of recombinant adenovirus-based vaccines to both birds and high-risk individuals in the face of an outbreak may serve to control the pandemic spread of lethal avian influenza.


2009 ◽  
Vol 83 (13) ◽  
pp. 6566-6577 ◽  
Author(s):  
Katherine A. Richards ◽  
Francisco A. Chaves ◽  
Andrea J. Sant

ABSTRACT The specificity of the CD4 T-cell immune response to influenza virus is influenced by the genetic complexity of the virus and periodic encounters with variant subtypes and strains. In order to understand what controls CD4 T-cell reactivity to influenza virus proteins and how the influenza virus-specific memory compartment is shaped over time, it is first necessary to understand the diversity of the primary CD4 T-cell response. In the study reported here, we have used an unbiased approach to evaluate the peptide specificity of CD4 T cells elicited after live influenza virus infection. We have focused on four viral proteins that have distinct intracellular distributions in infected cells, hemagglutinin (HA), neuraminidase (NA), nucleoprotein, and the NS1 protein, which is expressed in infected cells but excluded from virion particles. Our studies revealed an extensive diversity of influenza virus-specific CD4 T cells that includes T cells for each viral protein and for the unexpected immunogenicity of the NS1 protein. Due to the recent concern about pandemic avian influenza virus and because CD4 T cells specific for HA and NA may be particularly useful for promoting the production of neutralizing antibody to influenza virus, we have also evaluated the ability of HA- and NA-specific CD4 T cells elicited by a circulating H1N1 strain to cross-react with related sequences found in an avian H5N1 virus and find substantial cross-reactivity, suggesting that seasonal vaccines may help promote protection against avian influenza virus.


PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e31953 ◽  
Author(s):  
Sylvia S. N. Reemers ◽  
Daphne A. van Haarlem ◽  
Alice J. A. M. Sijts ◽  
Lonneke Vervelde ◽  
Christine A. Jansen

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Caroline Warren ◽  
Marek Slomka ◽  
Alejandro Nunez ◽  
Saumya Thomas ◽  
Sahar Mahmood ◽  
...  

The European H5N8 highly pathogenic avian influenza virus (HPAIV) epizootic during 2016-2017 resulted in both wild bird and poultry deaths throughout the EU. This in vivo study investigated the potential for indirect infection of naïve birds through contaminated drinking water or feed, to assess potential disease incursion into a high biosecurity commercial floor housed setting. Three-week-old Ross 308 chickens were exposed to H5N8 A/wigeon/Wales/52833/2016 (H5N8-2016) virus at a high (1 x 106 EID50/ml) or low (1 x 104 EID50/ml) dose, in either drinking water or feed for a 24 hour period. Chickens directly-infected with a high dose of H5N8-2016 (intra-nasal) acted as positive controls. Viral shedding, environmental contamination and clinical signs were monitored for ten days post infection (dpi). All directly-infected birds shed virus and were humanely terminated at 3 dpi. Immunohistochemical analysis of nasal epithelium and caecal tonsil lymphoid tissue, obtained at post mortem from directly-infected chickens (2 dpi), showed the presence of influenza antigen in both tissues. Only birds exposed to high dose virus in drinking water, shed virus and showed clinical disease presentation (67% mortality). Interestingly low levels of antigen were detected in the nasal epithelium, whereas higher levels were detected in the caecal tonsil. All surviving chickens from each group, remained uninfected and did not seroconvert. Our findings suggest virus bio availability in different substrates is variable (feed and water) and possible routes of viral contamination leading to disease ingress at poultry premises may have different outcomes including disease presentation.


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