A Recombinant Influenza A Virus Expressing Domain III of West Nile Virus Induces Protective Immune Responses against Influenza and West Nile Virus

Martina, Benedict; Doel, Petra van den; Koraka, Penelope; Amerongen, Geert van; Spohn, Gunther; Haagmans, Bart L.; Provacia, Lisette B.; Osterhaus, Albert D. M. E.; Rimmelzwaan, Guus F.

doi:10.1371/journal.pone.0018995

Cited by 37 publications

(30 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The capacity to engineer recombinant vaccines using a backbone different from the circulating IAV strains prevents neutralization by preexisting antibodies; an advantage of rIAV over many other recombinant live vectors. The feasibility of using rIAV as a vaccine vector has been confirmed for other viruses, such as HIV and SIV [36], respiratory syncytial virus [37], hepatitis C virus [38], and West Nile virus [39], as well as the intracellular pathogen, Leishmania major [40], and Plasmodium falciparum [41]. In addition, rIAV expressing the M. tuberculosis-specific ESAT-6 protein was generated by reassortment and despite having reduced virulence also protected guinea pigs against M. tuberculosis challenge with similar efficacy to BCG [42].…”

Section: Discussionmentioning

confidence: 96%

Epitope‐specific CD4⁺, but not CD8⁺, T‐cell responses induced by recombinant influenza A viruses protect against Mycobacterium tuberculosis infection

et al. 2014

View full text Add to dashboard Cite

Tuberculosis remains a global health problem, in part due to failure of the currently available vaccine, BCG, to protect adults against pulmonary forms of the disease. We explored the impact of pulmonary delivery of recombinant influenza A viruses (rIAVs) on the induction of Mycobacterium tuberculosis (M. tuberculosis)-specific CD4 + and CD8 + T-cell responses and the resultant protection against M. tuberculosis infection in C57BL/6 mice. Intranasal infection with rIAVs expressing a CD4 + T-cell epitope from the Ag85B protein (PR8.p25) or CD8 + T-cell epitope from the TB10.4 protein (PR8.TB10.4) generated strong T-cell responses to the M. tuberculosis-specific epitopes in the lung that persisted long after the rIAVs were cleared. Infection with PR8.p25 conferred protection against subsequent M. tuberculosis challenge in the lung, and this was associated with increased levels of poly-functional CD4 + T cells at the time of challenge. By contrast, infection with PR8.TB10.4 did not induce protection despite the presence of IFN-γ-producing M. tuberculosis-specific CD8 + T cells in the lung at the time of challenge and during infection. Therefore, the induction of pulmonary M. tuberculosis epitope-specific CD4 + , but not CD8 + T cells, is essential for protection against acute M. tuberculosis infection in the lung. Keywords: CD4 + T cells r Interferon-γ r Lung r Recombinant influenza A virus r TuberculosisAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionTuberculosis (TB) is still one of the major causes of death worldwide, and it is estimated that one-third of the world's population Correspondence: Dr. Manuela Flórido e-mail: m.florido@centenary.org.au is infected by Mycobacterium tuberculosis (M. tuberculosis; WHO 2012, http://www.who.int/tb/publications/global_report). The only vaccine currently used, BCG, although effective at protecting young children, fails to protect adults from the pulmonary form of the disease with efficacies that range from 0 to 80% [1]. The most advanced vaccine in human studies is MVA85A, a nonreplicative vaccinia viral vector expressing M. tuberculosis Ag85A, but the results of a phase II clinical trial showed no additional C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 780-793 Immunity to infection 781 protective effect of this vaccine over BCG against clinical TB or the acquisition of M. tuberculosis infection in infants [2]. The development of more effective vaccines is therefore essential. The immune response against primary infection with M. tuberculosis in a naïve host involves mostly CD4 + T cells so unsurprisingly anti-TB vaccines were initially designed to induce a strong CD4 + T-cell response. That was the case for BCG and subunit vaccines that are potent inducers of systemic anti-M. tuberculosis CD4 + T-cell responses [3]. Emerging evidence that CD8 + T cells also played a role in both the immune response to M. tuberculosis infection and in the vaccin...

show abstract

Section: Discussionmentioning

confidence: 96%

Epitope‐specific CD4⁺, but not CD8⁺, T‐cell responses induced by recombinant influenza A viruses protect against Mycobacterium tuberculosis infection

et al. 2014

View full text Add to dashboard Cite

show abstract

“…First, the vaccine induces neutralizing antibodies with a just single dose. Second, live influenza viruses induce mucosal immune responses [10,13,15,51] that may be important for protective immunity to SAR-CoV-2 [17,52]. Third, it might be possible to leverage additional influenza-virusengineering approaches such as those described in [11] to generate virions that express NA as well as RBD, and could serve as dual influenza-and SARS-CoV-2 vaccines.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, well-established influenza reverse genetics systems make it easy to incorporate foreign genes into the viral genome [8][9][10][11][12]. In pre-clinical animal models, influenza virions expressing foreign antigens induce antibodies against the causative agents of a variety of diseases, including West Nile virus, Bacillus anthracis, botulinum neurotoxin, and HIV [13][14][15][16]. Intranasal infection with influenza viruses induces mucosal immune responses not only within the respiratory tract, but also in mucosal surfaces distal from the site of immunization [15], which may prove important for SARS-CoV-2 [17].…”

Section: Introductionmentioning

confidence: 99%

Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice

Loes

Gentles

Greaney

et al. 2020

Preprint

View full text Add to dashboard Cite

An effective vaccine is essential to controlling the spread of SARS-CoV-2 virus. Here, we describe an influenza-virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 Spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:250). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for production of influenza vaccines.

show abstract

“…The different virus platforms allow the selection of a vector that has a similar tropism to that of the target virus (e.g., recombinant vaccinia virus for intradermal vaccination or recombinant influenza virus for targeting the respiratory tract mucosa [55], [56]). …”

Section: Experimental Vaccines For Junv and Lasvmentioning

confidence: 99%

Vaccination Strategies against Highly Pathogenic Arenaviruses: The Next Steps toward Clinical Trials

Ölschläger

Flatz

2013

PLoS Pathog

View full text Add to dashboard Cite

Vaccination is one of the most valuable weapons against infectious diseases and has led to a significant reduction in mortality and morbidity. However, for most viral hemorrhagic fevers caused by arenaviruses, no prophylactic vaccine is available. This is particularly problematic as these diseases are notoriously difficult to diagnose and treat. Lassa fever is globally the most important of the fevers caused by arenaviruses, potentially affecting millions of people living in endemic areas, particularly in Nigeria. Annually, an estimated 300,000 humans are infected and several thousands succumb to the disease. The successful development of the vaccine “Candid#1” against Junin virus, the causative agent of Argentine hemorrhagic fever, proved that an effective arenavirus vaccine can be developed. Although several promising studies toward the development of a Lassa fever vaccine have been published, no vaccine candidate has been tested in human volunteers or patients. This review summarizes the immunology and other aspects of existing experimental arenavirus vaccine studies, discusses the reasons for the lack of a vaccine, and proposes a plan for overcoming the final hurdles toward clinical trials.

show abstract

A Recombinant Influenza A Virus Expressing Domain III of West Nile Virus Induces Protective Immune Responses against Influenza and West Nile Virus

Cited by 37 publications

References 55 publications

Epitope‐specific CD4⁺, but not CD8⁺, T‐cell responses induced by recombinant influenza A viruses protect against Mycobacterium tuberculosis infection

Epitope‐specific CD4⁺, but not CD8⁺, T‐cell responses induced by recombinant influenza A viruses protect against Mycobacterium tuberculosis infection

Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice

Vaccination Strategies against Highly Pathogenic Arenaviruses: The Next Steps toward Clinical Trials

Contact Info

Product

Resources

About

A Recombinant Influenza A Virus Expressing Domain III of West Nile Virus Induces Protective Immune Responses against Influenza and West Nile Virus

Cited by 37 publications

References 55 publications

Epitope‐specific CD4+, but not CD8+, T‐cell responses induced by recombinant influenza A viruses protect against Mycobacterium tuberculosis infection

Epitope‐specific CD4+, but not CD8+, T‐cell responses induced by recombinant influenza A viruses protect against Mycobacterium tuberculosis infection

Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice

Vaccination Strategies against Highly Pathogenic Arenaviruses: The Next Steps toward Clinical Trials

Contact Info

Product

Resources

About

Epitope‐specific CD4⁺, but not CD8⁺, T‐cell responses induced by recombinant influenza A viruses protect against Mycobacterium tuberculosis infection

Epitope‐specific CD4⁺, but not CD8⁺, T‐cell responses induced by recombinant influenza A viruses protect against Mycobacterium tuberculosis infection