Cold-Adapted Pandemic 2009 H1N1 Influenza Virus Live Vaccine Elicits Cross-Reactive Immune Responses against Seasonal and H5 Influenza A Viruses

Jang, Yo Han; Byun, Young Ho; Lee, Yoon Jae; Lee, Yun Ha; Lee, Kwang Hee; Seong, Baik Lin

doi:10.1128/jvi.07149-11

Cited by 44 publications

(40 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…IIV is administered parenterally and predominantly induces humoral antibodies, which can neutralize only antigenically similar viruses. In contrast, LAIV administered intranasally mimics natural infection and therefore can induce a much broader immune response, which is supported by animal models and epidemiological studies [8][9][10][11][12]. In addition, LAIV induces mucosal immunity that prevents virus replication in upper respiratory tract and therefore prevents virus spread to contact persons.…”

mentioning

confidence: 97%

H7N9: can H7N3 live-attenuated influenza vaccine be used at the early stage of the pandemic?

Rudenko

Isakova–Sivak

Rekstin

2013

Expert Review of Vaccines

View full text Add to dashboard Cite

mentioning

confidence: 97%

H7N9: can H7N3 live-attenuated influenza vaccine be used at the early stage of the pandemic?

Rudenko

Isakova–Sivak

Rekstin

2013

Expert Review of Vaccines

View full text Add to dashboard Cite

“…Limiting CVB3 replication within the heart may be a promising strategy to decrease CVB3 pathogenicity, and one relatively recent method to eliminate tissue-tropic viral infection takes advantage of factors specifically expressed in the tropic tissue, including cellular microRNAs (miRNAs) (5)(6)(7). In addition, specific antiviral vaccines are widely used and effectively function to immunize human hosts against pathogens such as HBV, H1N1, and poliomyelitis (8)(9)(10)(11), and ways to generate effective memory immune responses against CVB3 will be important for protection against future infections.…”

mentioning

confidence: 99%

Coxsackievirus B3 Engineered To Contain MicroRNA Targets for Muscle-Specific MicroRNAs Displays Attenuated Cardiotropic Virulence in Mice

Yao

Wang

et al. 2015

J Virol

View full text Add to dashboard Cite

Coxsackievirus B3 (CVB3) is trophic for cardiac tissue and is a major causative agent for viral myocarditis, where local viral replication in the heart may lead to heart failure or even death. Recent studies show that inserting microRNA target sequences into the genomes of certain viruses can eradicate these viruses within local host tissues that specifically express the cognate microRNA. Here, we demonstrated both in vitro and in vivo that incorporating target sequences for miRNA-133 and -206 into the 5= untranslated region of the CVB3 genome ameliorated CVB3 virulence in skeletal muscle and myocardial cells that specifically expressed the cognate cellular microRNAs. Compared to wild-type CVB3, viral replication of the engineered CVB3 was attenuated in human TE671 (rhabdomyosarcoma) and L6 (skeletal muscle) cell lines in vitro that expressed high levels of miRNA-206. In the in vivo murine CVB3-infection model, viral replication of the engineered CVB3 was attenuated specifically in the heart that expressed high levels of both miRNAs, but not in certain tissues, which allowed the host to retain the ability to induce a strong and protective humoral immune response against CVB3. The results of this study suggest that a microRNA-targeting strategy to control CVB3 tissue tropism and pathogenesis may be useful for viral attenuation and vaccine development. IMPORTANCECoxsackievirus B3 (CVB3) is a major causative agent for viral myocarditis, and viral replication in the heart may lead to heart failure or even death. Limiting CVB3 replication within the heart may be a promising strategy to decrease CVB3 pathogenicity. miRNAs are ϳ21-nucleotide-long, tissue-specific endogenous small RNA molecules that posttranscriptionally regulate gene expression by imperfectly binding to the 3= untranslated region (UTR), the 5= UTR, or the coding region within a gene. In our study, muscle-specific miRNA targets (miRT) were incorporated into the CVB3 genome. Replication of the engineered viruses was restricted in the important heart tissue of infected mice, which reduced cardiac pathology and increased mouse survival. Meanwhile, replication ability was retained in other tissues, thus inducing a strong humoral immune response and providing long-term protection against CVB3 rechallenge. This study suggests that a microRNA-targeting strategy can potentially control CVB3 tissue tropism and pathogenesis and may be useful for viral attenuation and vaccine development. C oxsackievirus B3 (CVB3) is a clinically relevant infectious agent that causes viral myocarditis, pancreatitis, and aseptic meningitis. CVB3 is cardiotropic and efficiently replicates in the heart. We and others have shown in various animal models that CVB3 replication induces a direct cytopathic effect on infected cells, leading to tissue damage (1, 2). At present, there is no effective therapy against CVB3, and strategies to develop such a therapy are greatly desired (3, 4). Limiting CVB3 replication within the heart may be a promising strategy to decrease CVB3 pathoge...

show abstract

“…The intranasal administration of live-attenuated influenza vaccines adapted to replicate at lower physiological temperatures suited to the upper respiratory tract can induce a broader range of systemic and mucosal antibody and limited T cellmediated responses [28][29][30][31], show some protection against drifted seasonal [32] and highly pathogenic strains [28,33]. However, due to the potential risk of attenuated vaccine strains to replicate in the lower respiratory tract, those in greatest need of vaccination, infants and the elderly, are excluded from using these vaccines.…”

Section: Discussionmentioning

confidence: 99%

Establishment of functional influenza virus-specific CD8+ T cell memory pools after intramuscular immunization

Wang

Chua

Vega-Ramos

et al. 2015

Vaccine

View full text Add to dashboard Cite

The emergence of the avian-origin influenza H7N9 virus and its pandemic potential has highlighted the ever-present need to develop vaccination approaches to induce cross-protective immunity. In this study, we examined the establishment of cross-reactive CD8(+) T cell immunity in mice following immunization with live A/Puerto Rico/8/1934 (PR8; H1N1) influenza virus via two non-productive inoculation routes. We found that immunization via the intramuscular (IM) route established functional influenza-virus specific memory CD8(+) T cell pools capable of cross-reactive recall responses. Epitope-specific primary, memory and recall CD8(+) T-cell responses induced by the IM route, highly relevant to human influenza immunisations, were of comparable magnitude and quality to those elicited by the intraperitoneal (IP) priming, commonly used in mice. Furthermore, IM immunisation resulted in lower lung viral titres following heterologous challenge with A/Aichi/68 (X31; H3N2) compared to the IP route. Examining the ability of DCs from lymphoid organs to present viral antigen revealed that immune induction following IM immunization occurred in draining lymph nodes, while immunization via the IP route resulted in the priming of responses in distal lymphoid organs, indicative of a systemic distribution of antigen. No major differences in the pulmonary cytokine environment of immunized animals following X31 challenge were observed that could account for the improved heterologous protection induced by the IM route. However, while both routes induced similar levels of PR8-specific antibodies, higher levels of cross-reactive antibodies against X31 were induced following IM inoculation. Our data demonstrate how non-replicative routes of infection can induce efficient cross-reactive CD8(+) T cell responses and strong strain-specific antibody responses, with the additional benefit from IM priming of enhanced heterosubtypic antibody production.

show abstract

Cold-Adapted Pandemic 2009 H1N1 Influenza Virus Live Vaccine Elicits Cross-Reactive Immune Responses against Seasonal and H5 Influenza A Viruses

Cited by 44 publications

References 46 publications

H7N9: can H7N3 live-attenuated influenza vaccine be used at the early stage of the pandemic?

H7N9: can H7N3 live-attenuated influenza vaccine be used at the early stage of the pandemic?

Coxsackievirus B3 Engineered To Contain MicroRNA Targets for Muscle-Specific MicroRNAs Displays Attenuated Cardiotropic Virulence in Mice

Establishment of functional influenza virus-specific CD8+ T cell memory pools after intramuscular immunization

Contact Info

Product

Resources

About