Vaccine molecules targeting Xcr1 on cross-presenting DCs induce protective CD8+T-cell responses against influenza virus

2014 ◽  
Vol 45 (2) ◽  
pp. 624-635 ◽  
Author(s):  
Even Fossum ◽  
Gunnveig Grødeland ◽  
Dorothea Terhorst ◽  
Anders A. Tveita ◽  
Elisabeth Vikse ◽  
...  
2009 ◽  
Vol 182 (8) ◽  
pp. 4565-4571 ◽  
Author(s):  
Michael J. Palmowski ◽  
Mathew Parker ◽  
Kaushik Choudhuri ◽  
Christopher Chiu ◽  
Margaret F. C. Callan ◽  
...  

2006 ◽  
Vol 36 (11) ◽  
pp. 2951-2959 ◽  
Author(s):  
Nicole L. La Gruta ◽  
Peter C. Doherty ◽  
Stephen J. Turner

2006 ◽  
Vol 103 (8) ◽  
pp. 2764-2769 ◽  
Author(s):  
P. G. Thomas ◽  
S. A. Brown ◽  
W. Yue ◽  
J. So ◽  
R. J. Webby ◽  
...  

2021 ◽  
Author(s):  
Santosh Dhakal ◽  
Jeffrey Loube ◽  
Julia A. Misplon ◽  
Chia-Yun Lo ◽  
Patrick Creisher ◽  
...  

Current influenza vaccines, live-attenuated or inactivated, do not protect against antigenically novel influenza A viruses (IAVs) of pandemic potential, which has driven interest in development of universal influenza vaccines. Universal influenza vaccine candidates targeting highly conserved antigens of IAV nucleoprotein (NP) are promising as vaccines that induce T cell immunity, but concerns have been raised about the safety of inducing robust CD8 T cell responses in the lungs. Using a mouse model, we systematically evaluated effects of recombinant adenovirus vectors (rAd) expressing IAV NP (A/NP-rAd) or influenza B virus (IBV) NP (B/NP-rAd) on pulmonary inflammation and function after vaccination and following live IAV challenge. After A/NP-rAd or B/NP-rAd vaccination, female mice exhibited robust systemic and pulmonary vaccine-specific B cell and T cell responses and experienced no morbidity (e.g., body mass loss). Both in vivo pulmonary function testing and lung histopathology scoring revealed minimal adverse effects of intranasal rAd vaccination compared with unvaccinated mice. After IAV challenge, A/NP-rAd vaccinated mice experienced significantly less morbidity, had lower pulmonary virus titers, and developed less pulmonary inflammation than unvaccinated or B/NP-rAd vaccinated mice. Based on analysis of pulmonary physiology using detailed testing not previously applied to the question of T cell damage, mice protected by vaccination also had better lung function than controls. Results provide evidence that in this model, adenoviral universal influenza vaccine does not damage pulmonary tissue. In addition, adaptive immunity, in particular T-cell immunity in the lungs, does not cause damage when restimulated, but instead mitigates pulmonary damage following IAV infection. Importance: Respiratory viruses can emerge and spread rapidly, before vaccines are available. It would be a tremendous advance to use vaccines that protect against whole categories of viruses, such as universal influenza vaccines, without the need to predict which virus will emerge. Nucleoprotein (NP) of influenza virus provides a target conserved among strains and is a dominant T-cell target. In animals, vaccination to NP generates powerful T cell immunity and long-lasting protection against diverse influenza strains. Concerns have been raised, but not evaluated experimentally, that potent local T-cell responses might damage the lungs. We analyzed lung function in detail in the setting of such a vaccination. Despite CD8 T-cell responses in the lungs, lungs were not damaged and functioned normally after vaccination alone and were protected upon subsequent infection. This precedent provides important support for vaccines based on T-cell-mediated protection, currently being considered for both influenza and SARS-CoV-2 vaccines.


2009 ◽  
Vol 83 (15) ◽  
pp. 7619-7628 ◽  
Author(s):  
Amy Sexton ◽  
Robert De Rose ◽  
Jeanette C. Reece ◽  
Sheilajen Alcantara ◽  
Liyen Loh ◽  
...  

ABSTRACT There is an urgent need for human immunodeficiency virus (HIV) vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions, although the infections were asymptomatic. Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins. SIV-specific CD8 T-cell responses bearing the mucosal homing marker β7 integrin were induced by vaccination of naïve animals. Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection. Sequential vaccination with influenza virus-SIV recombinants of different subtypes (H1N1 followed by H3N2 or vice versa) produced only a limited boost in immunity, probably reflecting T-cell immunity to conserved internal proteins of influenza A virus. SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia. Although our results suggest that influenza virus-HIV vaccines hold promise for the induction of mucosal immunity to HIV, broader antigen cover will be needed to limit cytotoxic T-lymphocyte escape.


2014 ◽  
Vol 92 (7) ◽  
pp. 605-611 ◽  
Author(s):  
Matthew R Olson ◽  
Shirley GK Seah ◽  
Kathryn Edenborough ◽  
Peter C Doherty ◽  
Andrew M Lew ◽  
...  

Vaccine ◽  
2016 ◽  
Vol 34 (9) ◽  
pp. 1172-1179 ◽  
Author(s):  
Hyon-Xhi Tan ◽  
Brad P. Gilbertson ◽  
Sinthujan Jegaskanda ◽  
Sheilajen Alcantara ◽  
Thakshila Amarasena ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document