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Cited by 239Respiratory viral infections researchSARS-CoV-2 and COVID-19 ResearchVirology and Viral Diseases

Biological challenges and technological opportunities for respiratory syncytial virus vaccine development

Open access
Graham, Barney S.·2011·Immunological Reviews
DOI 10.1111/j.1600-065x.2010.00972.xPMC PMC3023887
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Abstract

Summary: Respiratory syncytial virus (RSV) is an important cause of respiratory disease causing high rates of hospitalizations in infants, significant morbidity in children and adults, and excess mortality in the elderly. Major barriers to vaccine development include early age of RSV infection, capacity of RSV to evade innate immunity, failure of RSV‐induced adaptive immunity to prevent reinfection, history of RSV vaccine‐enhanced disease, and lack of an animal model fully permissive to human RSV infection. These biological challenges, safety concerns, and practical issues have significantly prolonged the RSV vaccine development process. One great advantage compared to other difficult viral vaccine targets is that passively administered neutralizing monoclonal antibody is known to protect infants from severe RSV disease. Therefore, the immunological goals for vaccine development are to induce effective neutralizing antibody to prevent infection and to avoid inducing T‐cell response patterns associated with enhanced disease. Live‐attenuated RSV and replication‐competent chimeric viruses are in advanced clinical trials. Gene‐based strategies, which can control the specificity and phenotypic properties of RSV‐specific T‐cell responses utilizing replication‐defective vectors and which may improve on immunity from natural infection, are progressing through preclinical testing. Atomic level structural information on RSV envelope glycoproteins in complex with neutralizing antibodies is guiding design of new vaccine antigens that may be able to elicit RSV‐specific antibody responses without induction of RSV‐specific T‐cell responses. These new technologies may allow development of vaccines that can protect against RSV‐mediated disease in infants and establish a new immunological paradigm in the host to achieve more durable protection against reinfection.

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  • Currently there is no vaccine for RSV and, because of a history of disease enhancement upon natural infection after immunization with an RSV vaccine candidate that elicited TH2-biased (and non-neutralizing) RSV-specific immune responses in RSV-naive infants, elicitation of a non-TH2-biased RSV-specific response is considered an essential attribute for infant RSV vaccine candidates.

    “Currently there is no vaccine for RSV and, because of a history of disease enhancement upon natural infection after immunization with an RSV vaccine candidate that elicited T H 2-biased (and non-neutralizing) RSV-specific immune responses in RSV-naive infants, elicitation of a non-T H 2-biased RSV-specific response is considered an essential attribute for infant RSV vaccine candidates (33).”

    From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [33]

    The Major hurdles section says adequate RSV vaccine options were unavailable and describes enhanced disease in infants after the formalin-inactivated vaccine. The Vaccine-enhanced disease section reports poor neutralizing antibody responses in those children, and the Role of T cells in vaccine-enhanced illness section recommends avoiding Th2 responses in RSV vaccines. However, it identifies clear Th2 induction in immunized animal models, not as a directly established response in the infants; their lung eosinophilia is cited as a reason for concern. (LLM, conf=0.86)

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  • For infant RSV vaccine development, safety considerations favor replicating (or self-amplifying) vaccine candidates over subunit approaches.

    “However, for infant RSV vaccine development, safety considerations favor replicating (or selfamplifying) vaccine candidates over subunit approaches (33).”

    From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [33]

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Research works printed but not linked: 1

  1. [91]Collins PL Crowe JE Jr Knipe DM Griffin DE Lamb RA Martin MA Roizman B Straus SE Respiratory syncytial virus and metapneumovirus. Fields Virology 2007 1601 1646 Lippincott Williams & Wilkins Philadelphia, PA 5th edn.

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Authors
Graham, B. S.
Affiliations
National Institutes of Health (US)
Corresponding author
Graham, Barney S.
ORCID
Graham, Barney S.
Venue
Immunological Reviews
Publisher
Wiley
Published
2010-12-28
Volume
239
Issue
1
Pages
149-166
ISSN
  • 0105-2896 (ISSN-L)
  • 1600-065X
DOI
10.1111/j.1600-065x.2010.00972.x
PMC
PMC3023887
OpenAlex
W1547768824
Cited by
239
References
137
Citations by year
2026: 7 · 2025: 15 · 2024: 14 · 2023: 4 · 2022: 7 · 2021: 7 · 2020: 8 · 2019: 13 · 2018: 10 · 2017: 18 · 2016: 18 · 2015: 19 · 2014: 27 · 2013: 38 · 2012: 20
FWCI
2.60
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Immunological Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (ZIAAI005029, ZIAAI005027)
Topics
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords
respiratory syncytial virus, RSV vaccine development, vaccine-enhanced disease, neutralizing monoclonal antibodies, chimeric viruses, replication-defective vectors, T cell immunity, reinfection, innate immune evasion, infants
MeSH terms
Adult, Animals, Antibodies, Viral, Disease Models, Animal, T-Lymphocytes, Helper-Inducer, Humans, Infant, Infant, Newborn, Respiratory Syncytial Viruses, Vaccines, Attenuated, Respiratory Syncytial Virus Infections, CD8-Positive T-Lymphocytes, Vaccines, DNA, Respiratory Syncytial Virus Vaccines, Adaptive Immunity

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