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WHO collaborative studies on enterovirus reference antisera; fourth report.

Abstract: This paper summarizes the results of the fourth part of a comprehensive programme undertaken by the WHO International Reference Centre for Enteroviruses and other laboratories for the testing of enterovirus equine antisera prepared for long-term use as reference antisera. The studies were designed to appraise the specificity of the immune serum of horses inoculated with prototype enteroviruses (coxsackievirus types A2, 4, 8, 10, 11, 14-16, 18-21, and 24, and echoviruses E21, 27, 30, 31, and 33). Tests for neutralizing antibody were performed against the homologous viruses and against available regional homotypic strains. Heterotypic tests were performed against reoviruses 1-3, adenoviruses 1-31, and the entire series of enteroviruses (with the exception of enterovirus 68). The homologous geometric mean titre of the 5 echovirus antisera ranged from 3 000 to 10 000; the titre of 1 coxsackievirus antiserum (A24) was only about 400, but the titres of the others ranged from 1 500 to 14 000. All corresponding preinoculation sera were negative. Heterotypic antibody of significant titre was found in 4 antisera: E31 serum against E5 virus, CA8 serum against CA3 virus, CA13 serum against CA18 virus, and CA15 serum against CA2 virus. Information on other heterotypic antibody titres (where found) is recorded for guidance in the use of the sera. The results of homotypic tests with viruses isolated by the collaborating laboratories, though limited in number, were satisfactory.
Publication Date: 1973-01-01 PubMed ID: 4357975PubMed Central: PMC2481106
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  • Journal Article

Summary

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The research work involved a comprehensive testing program by the WHO’s International Reference Centre for Enteroviruses, aiming to assess the specificity of horse-generated immune serum created with specific prototype enteroviruses. Relevant virus strains were used for testing, and the tests aimed to discover how well the horse serum neutralized these.

Study Scope and Methodology

  • The program was devised to assess equine antisera for reference antisera use over a long period. The antisera were obtained from horses purposely inoculated with chosen enteroviruses.
  • Enteroviruses used for inoculation were of different types, essentially coxsackieviruses (e.g., types A2, A4, A8, A10, A11, A14-A16, A18-A21, and A24) and echoviruses (E21, E27, E30, E31, and E33).
  • The researchers used tests for neutralizing antibodies against the homologous viruses. In other words, tests were conducted to investigate whether the immune serum could neutralize the same type of virus used for inoculation.
  • In addition to these homologous tests, heterotypic tests were carried out, where the antisera were tested against different virus strains such as reoviruses 1-3, adenoviruses 1-31, and across the enteroviruses spectrum (except enterovirus 68).

Study Findings

  • The geometric mean titre for the 5 echovirus antisera ranged between 3,000 to 10,000. The geometric mean titre serves as a measure of the concentration of antibodies in the antisera. Higher concentration benefits the body’s immune response against the viruses.
  • The titre of one coxsackievirus antiserum (A24) was low at around 400, while it varied from 1,500 to 14,000 for others.
  • All corresponding pre-inoculation sera (before the horses were subjected to virus inoculation) were reported as negative, indicating the absence of significant neutralizing antibodies to these viruses before inoculation.
  • Four antisera demonstrated significant heterotypic antibody titre; these were E31 serum against E5 virus, CA8 serum against CA3 virus, CA13 serum against CA18 virus, and CA15 serum against CA2 virus. This indicates that these sera could also neutralize some different types of viruses.
  • Though limited in number, homotypic tests’ results against laboratory-isolated viruses were satisfactory.

Implications

  • The results of the study provide valuable information that can guide the usage of these antisera for treating the specific as well as some heterotypic viruses.
  • The successfully generated and robust antibodies against chosen viruses could be effectively employed in the diagnosis and therapeutic processes.

Cite This Article

APA
Melnick JL, Hampil B. (1973). WHO collaborative studies on enterovirus reference antisera; fourth report. Bull World Health Organ, 48(4), 381-396.

Publication

ISSN: 0042-9686
NlmUniqueID: 7507052
Country: Switzerland
Language: English
Volume: 48
Issue: 4
Pages: 381-396

Researcher Affiliations

Melnick, J L
    Hampil, B

      MeSH Terms

      • Adenoviridae / immunology
      • Animals
      • Antibodies, Heterophile / analysis
      • Antibody Specificity
      • Enterovirus / immunology
      • Enterovirus B, Human / immunology
      • Horses / immunology
      • Immune Sera
      • Reoviridae / immunology
      • World Health Organization

      References

      This article includes 12 references
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      Citations

      This article has been cited 6 times.
      1. Angez M, Shaukat S, Zahra R, Sharif S, Alam MM, Khurshid A, Rana MS, Zaidi SS. Identification of new genotype of Echovirus 19 from children with Acute Flaccid Paralysis in Pakistan.. Sci Rep 2015 Dec 8;5:17456.
        doi: 10.1038/srep17456pubmed: 26644348google scholar: lookup
      2. Takamatsu Y, Uchida L, Nga PT, Okamoto K, Nabeshima T, Thao DT, Hai do T, Tuyet NT, Duc HM, Luat le X, Hasebe F, Morita K. An approach for differentiating echovirus 30 and Japanese encephalitis virus infections in acute meningitis/encephalitis: a retrospective study of 103 cases in Vietnam.. Virol J 2013 Sep 11;10:280.
        doi: 10.1186/1743-422X-10-280pubmed: 24025733google scholar: lookup
      3. Zhou F, Kong F, McPhie K, Ratnamohan M, Gilbert GL, Dwyer DE. Molecular identification and analysis of nonserotypeable human enteroviruses.. J Clin Microbiol 2010 Apr;48(4):1276-82.
        doi: 10.1128/JCM.02384-09pubmed: 20164278google scholar: lookup
      4. Lin TL, Li YS, Huang CW, Hsu CC, Wu HS, Tseng TC, Yang CF. Rapid and highly sensitive coxsackievirus a indirect immunofluorescence assay typing kit for enterovirus serotyping.. J Clin Microbiol 2008 Feb;46(2):785-8.
        doi: 10.1128/JCM.01114-07pubmed: 18032614google scholar: lookup
      5. Mirkovic RR, Kono R, Yin-Murphy M, Sohier R, Schmidt NJ, Melnick JL. Enterovirus type 70: the etiologic agent of pandemic acute haemorrhagic conjunctivitis.. Bull World Health Organ 1973;49(4):341-6.
        pubmed: 4368683
      6. Melnick JL, Wimberly IL. Lyophilized combination pools of enterovirus equine antisera: new LBM pools prepared from reserves of antisera stored frozen for two decades.. Bull World Health Organ 1985;63(3):543-50.
        pubmed: 2994900