Induction of CD8 T Cell Heterologous Protection by a Single Dose of Single-Cycle Infectious Influenza Virus

Guo, Hailong; Baker, Steven F.; Martínez-Sobrido, Luis; Topham, David J.

doi:10.1128/jvi.01847-14

Cited by 28 publications

(35 citation statements)

References 50 publications

(61 reference statements)

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“…Furthermore, when mice were concomitantly administered M2SR and live wildtype influenza viruses, no replication-competent viruses containing M2SR segments were observed (Y. Hatta & P. Bilsel, unpublished data). The potential safety and advantages of single replication cycle vaccines over traditional live attenuated vaccines have been discussed elsewhere [23, 24]. Our data suggest that the protective cross-reactive responses elicited by M2SR H1N1 may be important in boosting these responses to mitigate a pandemic infection as has been suggested previously [25–27].…”

Section: Discussionsupporting

confidence: 75%

M2SR, a novel live influenza vaccine, protects mice and ferrets against highly pathogenic avian influenza

Hatta

Boltz

Sarawar

et al. 2017

Vaccine

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The emergence of highly pathogenic avian influenza H5N1 viruses has heightened global concern about the threat posed by pandemic influenza. To address the need for a highly effective universal influenza vaccine, we developed a novel M2-deficient single replication (M2SR) influenza vaccine virus and previously reported that it provided strong heterosubtypic protection against seasonal influenza viruses in mice. In the current study, we assessed M2SR induced protection against H5N1 influenza in mice and ferrets. Mice were intranasally inoculated with M2SR viruses containing the HA and NA from A/Vietnam/1203/2004 (M2SR H5N1) or A/California/07/2009 (M2SR H1N1). All M2SR vaccinated mice survived lethal challenge with influenza A/Vietnam/1203/2004 (H5N1), whereas 40% of mice vaccinated with recombinant H5 HA and none of the naïve controls survived. M2SR H5N1 provided sterile immunity, whereas low levels of virus were detected in the lungs of some M2SR H1N1 vaccinated mice. In contrast, recombinant H5 HA vaccinated mice and naïve controls showed systemic infection. M2SR H5N1 induced strong serum and mucosal antibody responses (IgG and IgA classes) against H5 HA, with high hemagglutination inhibition (HAI) titers. In contrast, while M2SR H1N1 elicited cross-reactive antibodies recognizing the H5 HA2 stalk region or the neuraminidase, no HAI activity against H5N1 virus was detected after M2SR H1N1 immunization. Both M2SR H5N1 and H1N1 also protected ferrets against lethal challenge with A/Vietnam/1203/2004. A prime-boost regimen provided optimal protection with no virus detected in the respiratory tract or brain after challenge. As in the mouse model, only the M2SR H5N1 vaccine induced HAI antibodies against the challenge virus in ferrets, while the M2SR H1N1 was able to provide protection without the induction of HAI antibodies. In summary, effective protection against highly pathogenic H5N1 influenza virus was provided by both homologous H5N1 M2SR and heterologous H1N1 M2SR demonstrating the cross-protective attributes of the M2SR platform.

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Section: Discussionsupporting

confidence: 75%

M2SR, a novel live influenza vaccine, protects mice and ferrets against highly pathogenic avian influenza

Hatta

Boltz

Sarawar

et al. 2017

Vaccine

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“…Similar to infection with WT IAV, LAIV immunization also leads to recruitment of influenza-specific CD8 T cells to the lungs (42,50,(52)(53)(54), which provides immunity against heterologous influenza challenge (42, 52). Thus, a LAIV rather than an IIV is desired for the control of IAV infections (22,23,27,55).…”

Section: Discussionmentioning

confidence: 99%

Temperature-Sensitive Live-Attenuated Canine Influenza Virus H3N8 Vaccine

Nogales

Rodríguez

Chauché

et al. 2017

J Virol

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Canine influenza is a respiratory disease of dogs caused by canine influenza virus (CIV). CIV subtypes responsible for influenza in dogs include H3N8, which originated from the transfer of H3N8 equine influenza virus to dogs; and the H3N2 CIV, which is an avian-origin virus that adapted to infect dogs. Influenza infections are most effectively prevented through vaccination to reduce transmission and future infection. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV in dogs. However, the efficacy of IIVs is suboptimal, and novel approaches are necessary for the prevention of disease caused by this canine respiratory pathogen. Using reverse genetics techniques, we have developed a live-attenuated CIV vaccine (LACIV) for the prevention of H3N8 CIV. The H3N8 LACIV replicates efficiently in canine cells at 33°C but is impaired at temperatures of 37 to 39°C and was attenuated compared to wild-type H3N8 CIV in vivo and ex vivo. The LACIV was able to induce protection against H3N8 CIV challenge with a single intranasal inoculation in mice. Immunogenicity and protection efficacy were better than that observed with a commercial CIV H3N8 IIV but provided limited cross-reactive immunity and heterologous protection against H3N2 CIV. These results demonstrate the feasibility of implementing a LAIV approach for the prevention and control of H3N8 CIV in dogs and suggest the need for a new LAIV for the control of H3N2 CIV. IMPORTANCE Two influenza A virus subtypes has been reported in dogs in the last 16 years: the canine influenza viruses (CIV) H3N8 and H3N2 of equine and avian origins, respectively. To date, only inactivated influenza vaccines (IIVs) are available to prevent CIV infections. Here, we report the generation of a recombinant, temperature-sensitive H3N8 CIV as a live-attenuated influenza vaccine (LAIV), which was attenuated in mice and dog tracheal, explants compared to CIV H3N8 wild type. A single dose of H3N8 LACIV showed immunogenicity and protection against a homologous challenge that was better than that conferred with an H3N8 IIV, demonstrating the feasibility of implementing a LAIV approach for the improved control of H3N8 CIV infections in dogs.

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“…Cells were grown at 37°C in a 5% CO 2 atmosphere. MDCK cells constitutively expressing influenza HA (MDCK-HA) from A/Brevig Mission/1/18 (H1N1; “1918”), A/WSN/33 (H1N1; “WSN”), A/Vietnam/1203/04 (H5N1; “Viet”), or from A/HongKong/1/1968 (H3N2; “X31”) were previously described [22, 28]. MDCK-HA cells stably expressing HA from influenza A/Indonesia/5/2005 (H5N1; “Indo”) were generated by co-transfecting the pCAGGS HA-expressing Indo plasmid and pCB7 (3:1 ratio) for eukaryotic expression of HA and Hygromycin B resistance, respectively [22, 29, 30].…”

Section: Methodsmentioning

confidence: 99%

Competitive detection of influenza neutralizing antibodies using a novel bivalent fluorescence-based microneutralization assay (BiFMA)

Baker

Nogales

Santiago

et al. 2015

Vaccine

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Avian-derived influenza A zoonoses are closely monitored and may be an indication of virus strains with pandemic potential. Both successful vaccination and convalescence of influenza A virus in humans typically results in the induction of antibodies that can neutralize viral infection. To improve long-standing and new-generation methodologies for detection of neutralizing antibodies, we have employed a novel reporter-based approach that allows for multiple antigenic testing within a single sample. Central to this approach is a single-cycle infectious influenza A virus (sciIAV), where a functional hemagglutinin (HA) gene was changed to encode either the green or the monomeric red fluorescent protein (GFP and mRFP, respectively) and HA is complemented in trans by stable HA-expressing cell lines. By using fluorescent proteins with non-overlapping emission spectra, this novel bivalent fluorescence-based microneutralization assay (BiFMA) can be used to detect neutralizing antibodies against two distinct influenza isolates in a single reaction, doubling the speed of experimentation while halving the amount of sera required. Moreover, this approach can be used for the rapid identification of influenza broadly neutralizing antibodies. Importantly, this novel BiFMA can be used for any given influenza HA-pseudotyped virus under BSL-2 facilities, including highly pathogenic influenza HA isolates.

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Induction of CD8 T Cell Heterologous Protection by a Single Dose of Single-Cycle Infectious Influenza Virus

Cited by 28 publications

References 50 publications

M2SR, a novel live influenza vaccine, protects mice and ferrets against highly pathogenic avian influenza

M2SR, a novel live influenza vaccine, protects mice and ferrets against highly pathogenic avian influenza

Temperature-Sensitive Live-Attenuated Canine Influenza Virus H3N8 Vaccine

Competitive detection of influenza neutralizing antibodies using a novel bivalent fluorescence-based microneutralization assay (BiFMA)

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