Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge

Bukreyev, Alexander; Marzi, Andrea; Feldmann, Friederike; Zhang, Liqun; Yang, Lijuan; Ward, Jerrold M.; Dorward, David W.; Pickles, Raymond J.; Murphy, Brian R.; Feldmann, Heinz; Collins, Peter L.

doi:10.1016/j.virol.2008.09.030

Cited by 61 publications

(60 citation statements)

References 39 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HPIV3/EboGP elicited greater levels of activated CD8 + and CD4 + T cells in lungs and blood, while in the spleen, levels were comparable between the 2 vaccines. Replication of the HPIV3/EboGP vaccine construct in the lungs of guinea pigs is attenuated by 63-to 200-fold compared with the wild-type vector (19,20), while the level of attenuation in NHPs is unknown. HPIV3/EboGP, whose replication is confined to the respiratory tract (18)(19)(20), likely stimulates antigenpresenting cells and induces T cell responses in bronchus-associated lymphoid tissues, as was demonstrated with influenza A virus in mice lacking spleens (48,49).…”

Section: Discussionmentioning

confidence: 99%

“…While aerosol particles less than 3 μM in diameter readily penetrate the small airways (26), the recipients of aerosolized HPIV3/EboGP received a 10-fold higher dose of the vaccine to account for a 10% delivery efficiency of aerosol particles to the lower respiratory tract in primate models due to small lung size and shallow breathing patterns (27,28) further exacerbated by anesthesia during vaccination (26). The VRP group was vaccinated by 2 sequential s.c. injections of 10 10 infecinto the vector particle and was functional in mediating infection of the respiratory tract, but did not alter the tropism of the vaccine virus (18)(19)(20). Rhesus macaques were protected against a lethal dose of EBOV when 2 successive liquid doses of the vaccine were administered using the combined intranasal and intratracheal (i.n./i.t.)…”

Section: Studymentioning

confidence: 99%

See 1 more Smart Citation

Aerosolized Ebola vaccine protects primates and elicits lung-resident T cell responses

Meyer¹,

Garrón²,

Lubaki³

et al. 2015

J. Clin. Invest.

Self Cite

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Studymentioning

confidence: 99%

Aerosolized Ebola vaccine protects primates and elicits lung-resident T cell responses

Meyer¹,

Garrón²,

Lubaki³

et al. 2015

J. Clin. Invest.

Self Cite

View full text Add to dashboard Cite

“…We previously evaluated HPIV3 (JS strain) expressing EBOV GP as an intranasal (i.n.) vaccine candidate called rHPIV3/EboGP (9,20,21). In NHPs, one i.n.…”

mentioning

confidence: 99%

Attenuated Human Parainfluenza Virus Type 1 Expressing Ebola Virus Glycoprotein GP Administered Intranasally Is Immunogenic in African Green Monkeys

Lingemann

Liu

Surman

et al. 2017

J Virol

Self Cite

View full text Add to dashboard Cite

The recent 2014-2016 Ebola virus (EBOV) outbreak prompted increased efforts to develop vaccines against EBOV disease. We describe the development and preclinical evaluation of an attenuated recombinant human parainfluenza virus type 1 (rHPIV1) expressing the membrane-anchored form of EBOV glycoprotein GP, as an intranasal (i.n.) EBOV vaccine. GP was codon optimized and expressed either as a full-length protein or as an engineered chimeric form in which its transmembrane and cytoplasmic tail (TMCT) domains were replaced with those of the HPIV1 F protein in an effort to enhance packaging into the vector particle and immunogenicity. GP was inserted either preceding the N gene (pre-N) or between the N and P genes (N-P) of rHPIV1 bearing a stabilized attenuating mutation in the P/C gene (C Δ170 ). The constructs grew to high titers and efficiently and stably expressed GP. Viruses were attenuated, replicating at low titers over several days, in the respiratory tract of African green monkeys (AGMs). Two doses of candidates expressing GP from the pre-N position elicited higher GP neutralizing serum antibody titers than the N-P viruses, and unmodified GP induced higher levels than its TMCT counterpart. Unmodified EBOV GP was packaged into the HPIV1 particle, and the TMCT modification did not increase packaging or immunogenicity but rather reduced the stability of GP expression during in vivo replication. In conclusion, we identified an attenuated and immunogenic i.n. vaccine candidate expressing GP from the pre-N position. It is expected to be well tolerated in humans and is available for clinical evaluation.IMPORTANCE EBOV hemorrhagic fever is one of the most lethal viral infections and lacks a licensed vaccine. Contact of fluids from infected individuals, including droplets or aerosols, with mucosal surfaces is an important route of EBOV spread during a natural outbreak, and aerosols also might be exploited for intentional virus spread. Therefore, vaccines that protect against mucosal as well as systemic inoculation are needed. We evaluated a version of human parainfluenza virus type 1 (HPIV1) bearing a stabilized attenuating mutation in the P/C gene (C Δ170 ) as an intranasal vaccine vector to express the EBOV glycoprotein GP. We evaluated expression from two different genome positions (pre-N and N-P) and investigated the use of vector packaging signals. African green monkeys immunized with two doses of the vector expressing GP from the pre-N position developed high titers of GP neutralizing serum antibodies. The attenuated vaccine candidate is expected to be safe and immunogenic and is available for clinical development.

show abstract

“…Since the impeding factor showed from an epidemiological investigation 60 that PEI to HPIV3 in the human adults may greatly impact the replication and immunogenicity of the vaccine, the vaccine vector was improved by deleting the HPIV3 F and HN genes, which are the main targets for the HPIV3-specific humoral immune response. 61 The new attenuated vector expressing EBOV-GP was more efficient in comparison to the previous construct. 61 One of the main advantages of the HPIV3-based vector platform is the potential for needle-free administration because of this vaccination via the respiratory route.…”

Section: Rvsv-ebovmentioning

confidence: 92%

“…61 The new attenuated vector expressing EBOV-GP was more efficient in comparison to the previous construct. 61 One of the main advantages of the HPIV3-based vector platform is the potential for needle-free administration because of this vaccination via the respiratory route. Safety is another virtue of HPIV3, triggered by restriction of virus only in epithelial cells of respiratory tract, an ongoing phase I clinical trial is carried out in US last year and this is one clinical trial which is given intranasally to human beings for now (NCT02564575) ( Table 1).…”

Section: Rvsv-ebovmentioning

confidence: 92%

Ebola vaccines in clinical trial: The promising candidates

Wang

et al. 2016

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

Ebola virus disease (EVD) has become a great threat to humans across the world in recent years. The 2014 Ebola epidemic in West Africa caused numerous deaths and attracted worldwide attentions. Since no specific drugs and treatments against EVD was available, vaccination was considered as the most promising and effective method of controlling this epidemic. So far, 7 vaccine candidates had been developed and evaluated through clinical trials. Among them, the recombinant vesicular stomatitis virusbased vaccine (rVSV-EBOV) is the most promising candidate, which demonstrated a significant protection against EVD in phase III clinical trial. However, several concerns were still associated with the Ebola vaccine candidates, including the safety profile in some particular populations, the immunization schedule for emergency vaccination, and the persistence of the protection. We retrospectively reviewed the current development of Ebola vaccines and discussed issues and challenges remaining to be investigated in the future.

show abstract

Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge

Cited by 61 publications

References 39 publications

Aerosolized Ebola vaccine protects primates and elicits lung-resident T cell responses

Aerosolized Ebola vaccine protects primates and elicits lung-resident T cell responses

Attenuated Human Parainfluenza Virus Type 1 Expressing Ebola Virus Glycoprotein GP Administered Intranasally Is Immunogenic in African Green Monkeys

Ebola vaccines in clinical trial: The promising candidates

Contact Info

Product

Resources

About