Live attenuated vaccines against influenza; an historical review

Wareing, Mark D.; Tannock, Gregory A.

doi:10.1016/s0264-410x(01)00045-7

Cited by 82 publications

(54 citation statements)

References 78 publications

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“…Such an interference phenomenon has been observed for multivalent, live attenuated influenza vaccine (29,30). Here, all three vaccine vectors were based on the same attenuated rVSV-N4CT1 vector; differing only in filovirus GP protein amino acid composition and structure.…”

Section: Discussionmentioning

confidence: 71%

Single-Dose Trivalent VesiculoVax Vaccine Protects Macaques from Lethal Ebolavirus and Marburgvirus Challenge

Matassov

Mire

Latham

et al. 2018

J Virol

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Previous studies demonstrated that a single intramuscular (i.m.) dose of an attenuated recombinant vesicular stomatitis virus (rVSV) vector (VesiculoVax vector platform; rVSV-N4CT1) expressing the glycoprotein (GP) from the Mayinga strain of Zaire ebolavirus (EBOV) protected nonhuman primates (NHPs) from lethal challenge with EBOV strains Kikwit and Makona. Here, we studied the immunogenicities of an expanded range of attenuated rVSV vectors expressing filovirus GP in mice. Based on data from those studies, an optimal attenuated trivalent rVSV vector formulation was identified that included rVSV vectors expressing EBOV, Sudan ebolavirus (SUDV), and the Angola strain of Marburg marburgvirus (MARV) GPs. NHPs were vaccinated with a single dose of the trivalent formulation, followed by lethal challenge 28 days later with each of the three corresponding filoviruses. At day 14 postvaccination, a serum IgG response specific for all three GPs was detected in all the vaccinated macaques. A modest and balanced cell-mediated immune response specific for each GP was also detected in a majority of the vaccinated macaques. No matter the level of total GP-specific immune response detected postvaccination, all the vaccinated macaques were protected from disease and death following lethal challenge with each of the three filoviruses. These findings indicate that vaccination with a single dose of attenuated rVSV-N4CT1 vectors each expressing a single filovirus GP may provide protection against the filoviruses most commonly responsible for outbreaks of hemorrhagic fever in sub-Saharan Africa.IMPORTANCE The West African Ebola virus Zaire outbreak in 2013 showed that the disease was not only a regional concern, but a worldwide problem, and highlighted the need for a safe and efficacious vaccine to be administered to the populace. However, other endemic pathogens, like Ebola virus Sudan and Marburg, also pose an important health risk to the public and therefore require development of a vaccine prior to the occurrence of an outbreak. The significance of our research was the development of a blended trivalent filovirus vaccine that elicited a balanced immune response when administered as a single dose and provided complete protection against a lethal challenge with all three filovirus pathogens.

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Section: Discussionmentioning

confidence: 71%

Single-Dose Trivalent VesiculoVax Vaccine Protects Macaques from Lethal Ebolavirus and Marburgvirus Challenge

Matassov

Mire

Latham

et al. 2018

J Virol

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“…The current trivalent inactivated influenza vaccines, administrated by subcutaneous injection, are used worldwide, yet their efficacies remain suboptimal, primarily because of inadequate stimulation of mucosal immunity in the upper respiratory tract, the site initially invaded by influenza viruses (23). Hence, these vaccines do not prevent viral infection; they only lessen the severity of the illness.…”

Section: Discussionmentioning

confidence: 99%

Generation of Influenza A Viruses with Chimeric (Type A/B) Hemagglutinins

Horimoto

Takada

Iwatsuki‐Horimoto

et al. 2003

J Virol

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To gain insight into the intertypic incompatibility between typeThe genomes of influenza A and B viruses each consist of eight single-stranded RNA segments of negative polarity. Both types of viruses have two envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). HA is responsible for viral binding to cellular sialic acid-containing receptors, followed by fusion between envelope and cell endosomal membranes, while NA is responsible for viral release from infected cells through removal of sialic acids from cellular glycoconjugates and viral glycoproteins (11). Type A viruses are further divided into subtypes based on HA (H1 to H15) and NA (N1 to N9) antigenicities. In cells infected with two different type A viruses, intratypic reassortants possessing various combinations of gene segments are produced (24). However, intertypic reassortants between type A and B viruses have not been detected in nature, although both viruses are cocirculating in human populations.Attempts to generate reassortants between type A and B viruses have been unsuccessful (9, 15, 21). With reverse genetics, Muster et al. (17) produced a mutant type A virus whose NA noncoding regions were replaced with those of the nonstructural (NS) gene of type B virus. This result suggests that at least the noncoding regions of the type B NS segment are compatible with influenza A viral components at the level of RNA transcription and replication. However, this mutant virus replicated more slowly than wild-type WSN virus in cell culture and was attenuated in mice (17). Animals infected with the chimeric virus were resistant to challenge with the wild-type virus, suggesting that such manipulation of the influenza virus genome might be useful in producing live attenuated vaccine strains.Recently, we established a plasmid-based reverse genetics system (18) that has provided a powerful tool for generating recombinant influenza viruses. To gain insight into the intertypic incompatibility between type A and B viruses, we used this technology to study the functionality of chimeric (A/B) HAs and then evaluated the potential of the chimeric (A/B) HA viruses as live vaccines. MATERIALS AND METHODSCells. 293T human embryonic kidney cells and COS-7 cells were maintained in Dulbecco's modified Eagle's medium with 10% fetal calf serum and antibiotics. Madin-Darby canine kidney (MDCK) cells were grown in minimal essential medium (MEM) with 5% newborn calf serum and antibiotics. Cells were maintained at 37°C in 5% CO 2 .Construction of plasmids. The generation of plasmid constructs for viral RNA production (pPolI), containing the HA genes of wild-type A/WSN/33 (H1N1, A/WSN) (pPolI-WSN-HA) and wild-type B/Lee/40 (B/Lee) (pPolI-B-HA) flanked by the human RNA polymerase I promoter and the mouse RNA polymerase I terminator, was described in a previous publication (18). A series of chimeric (A/B) HA pPolI constructs (Fig. 1) were produced with these wild-type HA constructs, PCR amplification with ProofStart polymerase (Qiagen), and ligation. Primer sequences will...

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“…Inactive influenza vaccines that are delivered by an intramuscular injection have been popularly used world-wide for the prevention of annual influenza epidemics. Alternatively, live vaccines are given by an intranasal route and are known to stimulates broader immunological response than the inactive vaccines providing cross-protective immune responses (Wareing and Tannock, 2001;Cox et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Reverse genetic platform for inactivated and live-attenuated influenza vaccine

2010

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Influenza vaccine strains have been traditionally developed by annual reassortment between vaccine donor strain and the epidemic virulent strains. The classical method requires screening and genotyping of the vaccine strain among various reassortant viruses, which are usually laborious and time-consuming. Here we developed an efficient reverse genetic system to generate the 6:2 reassortant vaccine virus from cDNAs derived from the influenza RNAs. Thus, cDNAs of the two RNAs coding for surface antigens, haemagglutinin and neuraminidase from the epidemic virus and the 6 internal genes from the donor strain were transfected into cells and the infectious viruses of 6:2 defined RNA ratio were rescued. X-31 virus (a high-growth virus in embryonated eggs) and its cold-adapted strain X-31 ca were judiciously chosen as donor strains for the generation of inactivated vaccine and live-attenuated vaccine, respectively. The growth properties of these recombinant viruses in embryonated chicken eggs and MDCK cell were indistinguishable as compared to those generated by classical reassortment process. Based on the reverse genetic system, we generated 6 + 2 reassortant avian influenza vaccine strains corresponding to the A/Chicken/Korea/ MS96 (H9N2) and A/Indonesia/5/2005 (H5N1). The results would serve as technical platform for the generation of both injectable inactivated vaccine and the nasal spray live attenuated vaccine for the prevention of influenza epidemics and pandemics.

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Live attenuated vaccines against influenza; an historical review

Cited by 82 publications

References 78 publications

Single-Dose Trivalent VesiculoVax Vaccine Protects Macaques from Lethal Ebolavirus and Marburgvirus Challenge

Single-Dose Trivalent VesiculoVax Vaccine Protects Macaques from Lethal Ebolavirus and Marburgvirus Challenge

Generation of Influenza A Viruses with Chimeric (Type A/B) Hemagglutinins

Reverse genetic platform for inactivated and live-attenuated influenza vaccine

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