scholarly journals A comparison of three vaccines against respiratory syncytial virus in calves

1984 ◽  
Vol 93 (2) ◽  
pp. 251-261 ◽  
Author(s):  
E. J. Stott ◽  
L. H. Thomas ◽  
G. Taylor ◽  
A. P. Collins ◽  
J. Jebbett ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Neutralizing Antibody ◽  
Temperature Sensitive ◽  
Virus Shedding ◽  
Live Vaccines ◽  
Bovine Strain ◽  
Nasal Swabs ◽  
Antibody Titres ◽  
The Mean ◽  
Syncytial Virus

SummaryAn inactivated vaccine against respiratory syncytial virus (RSV) was compared with two live vaccines. The inactivated (GC) vaccine consisted of glutaraldehyde-fixed bovine nasal mucosa cells persistently infected with RSV and emulsified with oil adjuvant. The live vaccines were a modified virus (MV) derived from a bovine strain of RSV and a temperature-sensitive mutant (ts-1) derived from a human strain. The GC vaccine was inoculated subcutaneously into 12 calves and the live vaccines intramuscularly into eight calves each. Nine unvaccinated calves acted as controls. The vaccines were administered in two doses 3 weeks apart and all calves were challenged intranasally with 2 × 107p.f.u. of bovine RSV 3 weeks after the second dose.At the time of challenge calves given GC, MV and ts-1 vaccines had mean serum neutralizing antibody titres of 25, 19 and 2 respectively; mean titres of IgG1antibody by radioimmunoassay were log104·5, 1·3 and 2·6 respectively and mean zone areas by single radial haemolysis (SRH) were 107, 27 and 36 mm2respectively.Eleven of 12 calves given GC vaccine were completely protected against challenge but all control animals and those given the two live vaccines were infected. The mean peak titre of virus in nasal swabs of control calves was 3.0 log10p.f.u./ml and the mean duration of virus shedding was 6·8 days. Both these parameters were significantly reduced in animals given MV and ts-1 vaccines: mean peak titres were 2·1 and 2·4 log10p.f.u./ml and mean duration of shedding was 3·4 and 3·3 days respectively.Thus, protection correlated better with RSV antibody detected by radio-immunoassay and SRH than with neutralizing antibody. These results are discussed in relation to the possible mechanism by which protection was mediated.

scholarly journals Shedding course of bovine respiratory syncytial virus and bovine parainfluenza 3 virus in calves vaccinated intranasally

2013 ◽  
Vol 57 (4) ◽  
pp. 479-483 ◽  
Author(s):  
Wojciech Socha ◽  
Jerzy Rola ◽  
Dariusz Bednarek ◽  
Renata Urban-Chmiel ◽  
Jan F. Żmudziński
Keyword(s):  
Respiratory Syncytial Virus ◽  
Specific Antibody ◽  
Bovine Respiratory Syncytial Virus ◽  
Parainfluenza Virus ◽  
Rt Pcr ◽  
Nasal Swabs ◽  
Before And After ◽  
Antibody Titres ◽  
Syncytial Virus ◽  
Bovine Parainfluenza Virus

Abstract Shedding time of bovine respiratory syncytial virus (BRSV) and bovine parainfluenza virus 3 (BPIV3) in calves vaccinated intranasally with modified live Rispoval RS-PI3 vaccine was determined. Blood and nasal swabs were collected on selected days before and after vaccination. Antibodies against BRSV and BPIV3 were tested by Respiratory ELISA Pentakit and the viral RNA was detected by RT-PCR. Twenty eight days after administration of the vaccine, a marked increase of specific antibody titres to BRSV and BPIV3 was detected in vaccinated calves. All animals were RT-PCR positive both for BRSV and BPIV3. Both viruses were excreted with nasal discharges within 8 d after vaccination but the course of shedding in individual calves was variable.

scholarly journals Safety and Immunogenicity of the Respiratory Syncytial Virus Vaccine RSV/ΔNS2/Δ1313/I1314L in RSV-Seronegative Children

2019 ◽  
Vol 222 (1) ◽  
pp. 82-91 ◽  
Author(s):  
Ruth A Karron ◽  
Cindy Luongo ◽  
Jocelyn San Mateo ◽  
Kimberli Wanionek ◽  
Peter L Collins ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Rational Design ◽  
Controlled Trial ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Temperature Sensitive ◽  
Double Blind ◽  
Respiratory Tract Illness ◽  
Syncytial Virus ◽  
Respiratory Syncytial Virus Vaccine

Abstract Background Respiratory syncytial virus (RSV) is the leading global cause of severe pediatric acute respiratory tract illness, and a vaccine is needed. RSV/ΔNS2/Δ1313/I1314L contains 2 attenuating elements: (1) deletion of the interferon antagonist NS2 gene and (2) deletion of codon 1313 of the RSV polymerase gene and the stabilizing missense mutation I1314L. This live vaccine candidate was temperature-sensitive, genetically stable, replication restricted, and immunogenic in nonhuman primates. Methods A single intranasal dose of RSV/ΔNS2/Δ1313/I1314L was evaluated in a double-blind, placebo-controlled trial (vaccine-placebo ratio, 2:1) at 106 plaque-forming units (PFU) in 15 RSV-seropositive children and at 105 and 106 PFU in 21 and 30 RSV-seronegative children, respectively. Results In RSV-seronegative children, the 105 PFU dose was overattenuated, but the 106 PFU dose was well tolerated, infectious (RSV/ΔNS2/Δ1313/I1314L replication detected in 90% of vaccinees), and immunogenic (geometric mean serum RSV plaque-reduction neutralizing antibody titer, 1:64). After the RSV season, 9 of 20 vaccinees had increases in the RSV titer that were significantly greater than those in 8 of 10 placebo recipients (1:955 vs 1:69, respectively), indicating that the vaccine primed for anamnestic responses after natural RSV exposure. Conclusion Rational design yielded a genetically stable candidate RSV vaccine that is attenuated yet immunogenic in RSV-seronegative children, warranting further evaluation. Clinical Trials Registration NCT01893554.

scholarly journals Evaluation of the Safety and Immune Efficacy of Recombinant Human Respiratory Syncytial Virus Strain Long Live Attenuated Vaccine Candidates

2021 ◽  
Author(s):  
Li-Nan Wang ◽  
Xiang-Lei Peng ◽  
Min Xu ◽  
Yuan-Bo Zheng ◽  
Yue-Ying Jiao ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Gene Deletion ◽  
Human Respiratory Syncytial Virus ◽  
Temperature Sensitive ◽  
T7 Promoter ◽  
Vaccine Candidates ◽  
Rsv Infection ◽  
Syncytial Virus

AbstractHuman respiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract illness (LRTI), and no vaccine against LRTI has proven to be safe and effective in infants. Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice. The constructed recombinant plasmids harbored (5′ to 3′) a T7 promoter, hammerhead ribozyme, RSV Long strain antigenomic cDNA with cold-passaged (cp) mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain (A2cpts) or further combined with SH gene deletion (A2cptsΔSH), HDV ribozyme (δ), and a T7 terminator. These vectors were subsequently co-transfected with four helper plasmids encoding N, P, L, and M2-1 viral proteins into BHK/T7-9 cells, and the recovered viruses were then passaged in Vero cells. The rescued recombinant RSVs (rRSVs) were named rRSV-Long/A2cp, rRSV-Long/A2cpts, and rRSV-Long/A2cptsΔSH, respectively, and stably passaged in vitro, without reversion to wild type (wt) at sites containing introduced mutations or deletion. Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed  temperature-sensitive (ts) phenotype in vitro and in vivo, all rRSVs were significantly attenuated in vivo. Furthermore, BALB/c mice immunized with rRSVs produced Th1-biased immune response, resisted wtRSV infection, and were free from enhanced respiratory disease. We showed that the combination of ΔSH with attenuation (att) mutations of cpts contributed to improving att phenotype, efficacy, and gene stability of rRSV. By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains, we have laid an important foundation for the development of RSV live attenuated vaccines.

scholarly journals Characterization of Pre-F-GCN4t, a Modified Human Respiratory Syncytial Virus Fusion Protein Stabilized in a Noncleaved Prefusion Conformation

2017 ◽  
Vol 91 (13) ◽  
Author(s):  
Normand Blais ◽  
Martin Gagné ◽  
Yoshitomo Hamuro ◽  
Patrick Rheault ◽  
Martine Boyer ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Human Respiratory Syncytial Virus ◽  
Vaccine Antigen ◽  
Significant Advance ◽  
F Protein ◽  
Syncytial Virus

ABSTRACT The human respiratory syncytial virus (hRSV) fusion (F) protein is considered a major target of the neutralizing antibody response to hRSV. This glycoprotein undergoes a major structural shift from the prefusion (pre-F) to the postfusion (post-F) state at the time of virus-host cell membrane fusion. Recent evidences suggest that the pre-F state is a superior target for neutralizing antibodies compared to the post-F state. Therefore, for vaccine purposes, we have designed and characterized a recombinant hRSV F protein, called Pre-F-GCN4t, stabilized in a pre-F conformation. To show that Pre-F-GCN4t does not switch to a post-F conformation, it was compared with a recombinant post-F molecule, called Post-F-XC. Pre-F-GCN4t was glycosylated and trimeric and displayed a conformational stability different from that of Post-F-XC, as shown by chemical denaturation. Electron microscopy analysis suggested that Pre-F-GCN4t adopts a lollipop-like structure. In contrast, Post-F-XC had a typical elongated conical shape. Hydrogen/deuterium exchange mass spectrometry demonstrated that the two molecules had common rigid folding core and dynamic regions and provided structural insight for their biophysical and biochemical properties and reactivity. Pre-F-GCN4t was shown to deplete hRSV-neutralizing antibodies from human serum more efficiently than Post-F-XC. Importantly, Pre-F-GCN4t was also shown to bind D25, a highly potent monoclonal antibody specific for the pre-F conformation. In conclusion, this construct presents several pre-F characteristics, does not switch to the post-F conformation, and presents antigenic features required for a protective neutralizing antibody response. Therefore, Pre-F-GCN4t can be considered a promising candidate vaccine antigen. IMPORTANCE Human respiratory syncytial virus (RSV) is a global leading cause of infant mortality and adult morbidity. The development of a safe and efficacious RSV vaccine remains an important goal. The RSV class I fusion (F) glycoprotein is considered one of the most promising vaccine candidates, and recent evidences suggest that the prefusion (pre-F) state is a superior target for neutralizing antibodies. Our study presents the physicochemical characterization of Pre-F-GCN4t, a molecule designed to be stabilized in the pre-F conformation. To confirm its pre-F conformation, Pre-F-GCN4t was analyzed in parallel with Post-F-XC, a molecule in the post-F conformation. Our results show that Pre-F-GCN4t presents characteristics of a stabilized pre-F conformation and support its use as an RSV vaccine antigen. Such an antigen may represent a significant advance in the development of an RSV vaccine.

scholarly journals Evolution of protection after maternal immunization for respiratory syncytial virus in cotton rats

2021 ◽  
Author(s):  
Jorge C.G. Blanco ◽  
Lori McGinnes-Cullen ◽  
Arash Kamali ◽  
Fatoumata Sylla ◽  
Marina Boukhavalova ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Neutralizing Antibody ◽  
Wild Type ◽  
Cotton Rat ◽  
Before And After ◽  
Boost Immunization ◽  
Cotton Rats ◽  
Antibody Titers ◽  
Syncytial Virus ◽  
Efficient Transfer

Maternal anti-respiratory syncytial virus (RSV) antibodies acquired by the fetus through the placenta protect neonates from RSV disease through the first weeks of life.  In the cotton rat model of RSV infections, we previously reported that immunization of dams during pregnancy with virus-like particles assembled with mutation stabilized pre-fusion F protein as well as the wild type G protein resulted in robust protection of their offspring from RSV challenge (Blanco, et al Journal of Virology 93: e00914-19, https://doi.org/10.1128/JVI.00914-19).  Here we describe the durability of those protective responses in dams, the durability of protection in offspring, and the transfer of that protection to offspring of two consecutive pregnancies without a second boost immunization.  We report that four weeks after birth, offspring of the first pregnancy were significantly protected from RSV replication in both lungs and nasal tissues after RSV challenge, but protection was reduced in pups at 6 weeks after birth.   However, the overall protection of offspring of the second pregnancy was considerably reduced, even at four weeks of age.  This drop in protection occurred even though the levels of total anti-pre-F IgG and neutralizing antibody titers in dams remained at similar, high levels before and after the second pregnancy.  The results are consistent with an evolution of antibody properties in dams to populations less efficiently transferred to offspring or the less efficient transfer of antibodies in elderly dams.

scholarly journals 2855. Respiratory Syncytial Virus Neutralizing Antibodies in Cord Blood and Serum from Infants up to 2 Years of Age in a Multinational Prospective Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S74-S75
Author(s):  
Joseph B Domachowske ◽  
Veronique Bianco ◽  
Ana Ceballos ◽  
Luis Cousin ◽  
Ulises D’Andrea ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Cord Blood ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Entire Cohort ◽  
Syncytial Virus ◽  
Tract Infections

Abstract Background Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections (LRTI) during infancy worldwide. High cord blood (CB) concentrations of anti-RSV neutralizing antibody (nAb) may attenuate, delay, or prevent infant infection. We report RSV A and B nAb concentrations in CB and serum from a birth cohort at different time points through 2 years of age. Methods Between 2013 and 2017, newborns from 8 countries were studied prospectively from birth to 2 years of age (NCT01995175). CB was collected at birth for the entire cohort. A subcohort of children was randomly assigned to have one blood sample collected again at either 2, 4, 6, 12, 18, or 24 months of age. Sera were analyzed for RSV A and B nAb concentrations by serum neutralization assay. Active surveillance was used to identify LRTIs during the 2-year follow-up as previously reported. Results In total, 2,401 newborns were enrolled and followed up. >99% of infants had detectable CB RSV A and B nAb. Geometric mean antibody titers (GMTs) varied by country, but were overall higher for RSV B than for RSV A (327 vs. 251; Figure 1). The lowest GMTs were seen from CB sera collected from South African newborns (197 RSV A, 255 RSV B); Canadian newborns had the highest RSV A GMT (383), while Hondurans had the highest RSV B GMT (460). 1380 infants provided follow-up serum nAb results as part of the subcohort (Figure 2). Dramatic waning of GMTs was evident, with a ~3-fold drop in GMTs at 2 months of age, and an additional ~2-fold drop between 2 and 4 months of age. At 6 and 12 months of age, 71% and 50% of infants had RSV A nAb and GMTs were at a nadir of 14. At 6, 12, and 18 months of age, RSV B nAb was detected in 98%, 69%, and 63% of infants, respectively. The RSV B nAb nadir GMT of 20 was observed at 12 months of age, while the 6- and 18-month RSV B nAb GMTs were 30 and 31, respectively. A total of 1,017 LRTIs were identified during the 2-year study period; of which, 94 (9%) were caused by RSV A and 132 (13%) by RSV B. Associations between CB nAb levels and RSV infection will be presented. Conclusion Neutralizing Ab to RSV A and B was present at birth in infants from 8 countries, and waned over time. GMTs were at a nadir at 6 to 12 months of age. Funding. GlaxoSmithKline Biologicals SA. Disclosures All Authors: No reported Disclosures.

scholarly journals Immunogenicity and Safety of 3 Formulations of a Respiratory Syncytial Virus Candidate Vaccine in Nonpregnant Women: A Phase 2, Randomized Trial

2019 ◽  
Vol 220 (11) ◽  
pp. 1816-1825 ◽  
Author(s):  
Tino F Schwarz ◽  
Roderick A McPhee ◽  
Odile Launay ◽  
Geert Leroux-Roels ◽  
Jaak Talli ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Candidate Vaccine ◽  
Phase 2 ◽  
Serious Adverse Events ◽  
Intramuscular Dose ◽  
Syncytial Virus ◽  
Neonates And Infants

Abstract Background Respiratory syncytial virus (RSV) is a common cause of respiratory tract illness and hospitalization in neonates and infants. RSV vaccination during pregnancy may protect offspring in their first months of life. Methods This randomized, observer-blind, multicenter, phase 2 study evaluated the immunogenicity and safety of an RSV candidate vaccine in healthy nonpregnant women aged 18–45 years. Four hundred participants were randomized (1:1:1:1) to receive a single intramuscular dose of vaccine containing 30 µg, 60 µg, or 120 µg of RSV fusion protein engineered to preferentially maintain a prefusion conformation (RSV-PreF vaccine) or placebo. Results Thirty days postvaccination, RSV-A neutralizing antibody geometric mean titers (GMTs) increased 3.75-, 4.42- and 4.36-fold; RSV-B neutralizing antibody GMTs 2.36-, 2.54- and 2.76-fold; and palivizumab competing antibody (PCA) concentrations 11.69-, 14.38- and 14.24-fold compared with baseline levels in the 30 µg, 60 µg, and 120 µg RSV-PreF groups, respectively. Antibody titers and PCA concentrations at day 30 were significantly higher with the 120 µg compared to the 30 µg RSV-PreF vaccine. All RSV-PreF vaccine formulations and the placebo had similar reactogenicity profiles. No serious adverse events were considered to be related to the RSV-PreF vaccine. Conclusions The 3 formulations of the investigational RSV-PreF vaccine were well-tolerated and induced RSV-A and RSV-B neutralizing antibodies and PCAs in healthy, nonpregnant women. Clinical Trials Registration NCT02956837.

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