Nonreplicating Vaccines Can Protect African Green Monkeys From the Memphis 37 Strain of Respiratory Syncytial Virus

Eyles, Jim E.; Johnson, J. Erik; Megati, Shakuntala; Roopchand, Vidia; Cockle, Paul; Weeratna, Risini D.; Makinen, Shawn R.; Brown, Tom; Lang, Susanne; Witko, Susan E.; Kotash, Cheryl S.; Li, Julia; West, Kate; Maldonado, Oscar; Falconer, Derek J.; Lees, Clare; Smith, George J.; White, Phil; Wright, Paul A.; Loudon, Peter T.; Merson, James; Jansen, Kathrin U.; Sidhu, Maninder K.

doi:10.1093/infdis/jit169

Cited by 14 publications

(14 citation statements)

References 33 publications

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“…In summary, the striking efficacy observed with the systemic DNA prime-tonsillar booster immunization regimen is, to our knowledge, superior to previous studies using DNA of AdV vaccines against hRSV in comparable NHP-animal models (14,15,54) and exhibits levels of viral reduction comparable to that achieved with Sendai virus vaccine or with chimeric parainfluenzavirus expressing hRSV antigens (55)(56)(57). Our results therefore suggest that the novel DNA prime-tonsillar booster regimen is a promising vaccine approach against hRSV and other respiratory viruses that should be pursued further.…”

Section: Discussionmentioning

confidence: 64%

Novel Vaccine Regimen Elicits Strong Airway Immune Responses and Control of Respiratory Syncytial Virus in Nonhuman Primates

Grünwald

Tenbusch

Schulte

et al. 2014

J Virol

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Induction of long-lasting immunity against viral respiratory tract infections؉ and CD8 ؉ T cell response in the lower respiratory tract and protection from intranasal hRSV challenge. Thus, parenteral DNA priming followed by booster immunization targeted to a mucosal inductive site constitutes an effective vaccine regimen for eliciting protective immune responses at mucosal effector sites. IMPORTANCEThe human respiratory syncytial virus (hRSV) is the most common cause of severe respiratory tract disease in infancy and leads to substantial morbidity and morality in the elderly. In this study, we compared the immunogenicity and efficacy of several genebased immunization protocols in rhesus macaques. Thereby, we found that the combination of an initially parenterally delivered DNA vaccine with a subsequent atraumatic tonsillar adenoviral vector immunization results in a strong systemic immune response accompanied by an exceptional high T-cell response in the mucosa. Strikingly, these animals were protected against a RSV challenge infection controlling the viral replication indicated by a 1,000-fold-lower viral load in the lower respiratory tract. Since mucosal cellular responses of this strength had not been described in earlier RSV vaccine studies, this heterologous DNA prime-tonsillar boost vaccine strategy is very promising and should be pursued for further preclinical and clinical testing.

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Section: Discussionmentioning

confidence: 64%

Novel Vaccine Regimen Elicits Strong Airway Immune Responses and Control of Respiratory Syncytial Virus in Nonhuman Primates

Grünwald

Tenbusch

Schulte

et al. 2014

J Virol

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“…African green monkeys (AGMs), which are semi-permissive for hRSV replication (Table 1), have been used in a number of studies to evaluate hRSV vaccine candidates [36], [37], [38], [39], [40], [41]. Clinical signs of disease are uncommon following hRSV infection, and AGMs develop only mild histopathological changes in the lung [38], [42], [43], The proportion of neutrophils in BAL of monkeys infected with the Memphis M37 (M37) strain of hRSV increased only to 9%, [40], whereas neutrophils are the predominant cell in BAL from hRSV-infected children [14].…”

Section: Animal Models Of Rsvmentioning

confidence: 99%

“…Clinical signs of disease are uncommon following hRSV infection, and AGMs develop only mild histopathological changes in the lung [38], [42], [43], The proportion of neutrophils in BAL of monkeys infected with the Memphis M37 (M37) strain of hRSV increased only to 9%, [40], whereas neutrophils are the predominant cell in BAL from hRSV-infected children [14].…”

Section: Animal Models Of Rsvmentioning

confidence: 99%

Animal models of respiratory syncytial virus infection

Taylor

2017

Vaccine

163

150

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“…The virus has been used for studies of human RSV disease [3], [4] and the clinical testing of disease inhibitory drugs including anti-inflammatory immunomodulators and passively-transferred antibodies (e.g. MEDI-557 by MedImmune LLC [ClinicalTrials.gov identifier NCT01475305], ALS-008176 by Alios Biopharma, Inc. [ClinicalTrials.gov identifier NCT02094365], ALN-RSV01 by Alnylam Pharmaceuticals [ClinicalTrials.gov identifier NCT00496821], GS-5806 by Gilead Sciences [5], and RV568 by Respivert Ltd. [ClinicalTrials.gov identifier NCT01230645]), as well as pre-clinical research [4], [6]–[10]. Based on results from human adult tests with RSV Memphis-37, antiviral drug products are gaining regulatory approval for testing in high-risk adult populations, infants and children.…”

Section: Introductionmentioning

confidence: 99%

Respiratory Syncytial Virus Human Experimental Infection Model: Provenance, Production, and Sequence of Low-Passaged Memphis-37 Challenge Virus

et al. 2014

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Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in children and is responsible for as many as 199,000 childhood deaths annually worldwide. To support the development of viral therapeutics and vaccines for RSV, a human adult experimental infection model has been established. In this report, we describe the provenance and sequence of RSV Memphis-37, the low-passage clinical isolate used for the model's reproducible, safe, experimental infections of healthy, adult volunteers. The predicted amino acid sequences for major proteins of Memphis-37 are compared to nine other RSV A and B amino acid sequences to examine sites of vaccine, therapeutic, and pathophysiologic interest. Human T- cell epitope sequences previously defined by in vitro studies were observed to be closely matched between Memphis-37 and the laboratory strain RSV A2. Memphis-37 sequences provide baseline data with which to assess: (i) virus heterogeneity that may be evident following virus infection/transmission, (ii) the efficacy of candidate RSV vaccines and therapeutics in the experimental infection model, and (iii) the potential emergence of escape mutants as a consequence of experimental drug treatments. Memphis-37 is a valuable tool for pre-clinical research, and to expedite the clinical development of vaccines, therapeutic immunomodulatory agents, and other antiviral drug strategies for the protection of vulnerable populations against RSV disease.

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Nonreplicating Vaccines Can Protect African Green Monkeys From the Memphis 37 Strain of Respiratory Syncytial Virus

Abstract: This study has validated the use of RSV (Memphis 37) in an African green monkey model of intranasal infection and identified nonreplicating vaccines capable of eliciting protection in this higher species challenge model.

Cited by 14 publications

References 33 publications

Novel Vaccine Regimen Elicits Strong Airway Immune Responses and Control of Respiratory Syncytial Virus in Nonhuman Primates

Novel Vaccine Regimen Elicits Strong Airway Immune Responses and Control of Respiratory Syncytial Virus in Nonhuman Primates

Animal models of respiratory syncytial virus infection

Respiratory Syncytial Virus Human Experimental Infection Model: Provenance, Production, and Sequence of Low-Passaged Memphis-37 Challenge Virus

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