Studies on human anti-rabies immunization in Brazil: II - Preliminary evaluation of the 2-1-1 schedule for human pre-exposure anti-rabies immunization, employing suckling mouse brain vaccine

Zanetti, Carlos Roberto; Lee, Luiza Marny; Chaves, Luciana Botelho; Rodrigues, José Luiz; Eleutério, Gilton C; Pereira, Octavio Augusto de C.

doi:10.1590/S0036-46651995000400012

Abstracts

This study reports preliminary results of virus neutralizing antibody (VNA) titers obtained on different days in the course of human anti-rabies immunization with the 2-1-1 schedule (one dose is given in the right arm and one dose in the left arm at day 0, and one dose is apllied on days 7 and 21), recommended by WHO for post-exposure treatment with cell culture vaccines. A variant schedule (double dose on day zero and another on day 14) was also tested, both employing suckling mouse brain vaccine. A complete seroconversion rate was obtained after only 3 vaccine doses, and almost all patients (11 of 12) presented titers higher than 1.0 IU/ml. Both neutralizing response and seroconversion rates were lower in the group receiving only 3 doses, regardless of the sample collecting day. Although our results are lower than those found with cell culture vaccines, the geometry mean of VNA is fully satisfactory, overcoming the lower limit recommended by WHO of 0.5 IU/ml. The 2-1-1 schedule could be an alternative one for pre exposure immunization, shorter than the classical 3+1 regimen (one dose on days 0, 2, 4 and 30) with only three visits to the doctor, instead of four.

Rabies; Human pre-exposure vaccination; 2-1-1 schedule; Mouse brain vaccine

Este estudo apresenta resultados preliminares de títulos de anticorpos neutralizantes (AcN) obtidos em diferentes dias durante imunização anti-rábica humana empregando o esquema 2-1-1 (uma dose administrada em cada deltóide no dia 0, e uma dose nos dias 7 e 21), recomendado pela OMS para tratamento pós-exposição com vacinas de cultivo celular. Um esquema variante (dose dupla no dia zero e outra no dia 14) também foi testado; em ambos esquemas utilizamos a vacina produzida em cérebro de camundongos recém-nascidos. Obteve-se taxa de soroconversão total após 3 doses de vacina, e quase todos os pacientes (11 de 12) apresentaram títulos maiores que 1,0 UI/ml. Tanto os títulos de anticorpos neutralizantes como a taxa de soroconversão foram menores no grupo que recebeu apenas 3 doses, independentemente do dia da coleta de soro. Embora nossos resultados tenham sido inferiores àqueles encontrados com vacinas de cultivo celular, a média geométrica de AcN foi inteiramente satisfatória, sobrepondo o limite mínimo de 0,5 UI/ml recomendado pela OMS. O esquema 2-1-1 pode ser alternativa para tratamento pré-exposição: mais curto que o esquema clássico 3 + 1 (uma dose nos dias 0, 2, 4 e 30) e com apenas três idas ao médico, ao invés de quatro.

VACCINE STUDIES

Studies on human anti-rabies immunization in Brazil. II - Preliminary evaluation of the 2-1-1 schedule for human pre-exposure anti-rabies immunization, employing suckling mouse brain vaccine

Estudos sobre imunização anti-rábica humana no Brasil. II - Avaliação preliminar do esquema 2-1-1 para imunização anti-rábica humana pré-exposição, empregando vacina de tecido nervoso de camundongos recém-nascidos

Carlos Roberto Zanetti^I; Luiza Marny Lee^I; Luciana Botelho Chaves^I; José Luiz Rodrigues^II; Gilton C. Eleutério^II; Octavio Augusto de C. Pereira^I

^IInstituto Pasteur - São Paulo, SP, Brazil

^IILaboratório Biovet S.A.

^{Correspondence to} Correspondence to: Carlos Roberto Zanetti (PhD) Instituto Pasteur Av. Paulista, 393 01311-000 São Paulo, SP, Brazil FAX: 55.11.289-0831

SUMMARY

This study reports preliminary results of virus neutralizing antibody (VNA) titers obtained on different days in the course of human anti-rabies immunization with the 2-1-1 schedule (one dose is given in the right arm and one dose in the left arm at day 0, and one dose is apllied on days 7 and 21), recommended by WHO for post-exposure treatment with cell culture vaccines. A variant schedule (double dose on day zero and another on day 14) was also tested, both employing suckling mouse brain vaccine. A complete seroconversion rate was obtained after only 3 vaccine doses, and almost all patients (11 of 12) presented titers higher than 1.0 IU/ml. Both neutralizing response and seroconversion rates were lower in the group receiving only 3 doses, regardless of the sample collecting day. Although our results are lower than those found with cell culture vaccines, the geometry mean of VNA is fully satisfactory, overcoming the lower limit recommended by WHO of 0.5 IU/ml. The 2-1-1 schedule could be an alternative one for pre exposure immunization, shorter than the classical 3+1 regimen (one dose on days 0, 2, 4 and 30) with only three visits to the doctor, instead of four.

Keywords: Rabies; Human pre-exposure vaccination; 2-1-1 schedule; Mouse brain vaccine.

RESUMO

Este estudo apresenta resultados preliminares de títulos de anticorpos neutralizantes (AcN) obtidos em diferentes dias durante imunização anti-rábica humana empregando o esquema 2-1-1 (uma dose administrada em cada deltóide no dia 0, e uma dose nos dias 7 e 21), recomendado pela OMS para tratamento pós-exposição com vacinas de cultivo celular. Um esquema variante (dose dupla no dia zero e outra no dia 14) também foi testado; em ambos esquemas utilizamos a vacina produzida em cérebro de camundongos recém-nascidos. Obteve-se taxa de soroconversão total após 3 doses de vacina, e quase todos os pacientes (11 de 12) apresentaram títulos maiores que 1,0 UI/ml. Tanto os títulos de anticorpos neutralizantes como a taxa de soroconversão foram menores no grupo que recebeu apenas 3 doses, independentemente do dia da coleta de soro. Embora nossos resultados tenham sido inferiores àqueles encontrados com vacinas de cultivo celular, a média geométrica de AcN foi inteiramente satisfatória, sobrepondo o limite mínimo de 0,5 UI/ml recomendado pela OMS. O esquema 2-1-1 pode ser alternativa para tratamento pré-exposição: mais curto que o esquema clássico 3 + 1 (uma dose nos dias 0, 2, 4 e 30) e com apenas três idas ao médico, ao invés de quatro.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

ACKNOWLEDGEMENTS

The authors gratefully acknowledge Mrs. Dolores Ayako Yoda for technical assistence.

Recebido para publicação em 06/02/1995

Aceito para publicação em 06/04/1995

1. ALBAS, A.; MOURĂO FUCHES, R.M.; FRAZATTI GALLINA, N.M. et al. - Termoestabilidade da vacina contra raiva, tipo Fuenzalida & Palacios, uso humano. Rev. Inst. Med. trop. S.Paulo, 34: 27-31, 1992.
2. CHAMELET, E.L.B.; AZEVEDO, M.P.; FAVORETTO, S.R.; KERBRIE, S.V. & SOUZA, L.T.M. - Esquema reduzido de vacinaçăo anti-rábica humana pré-exposiçăo e avaliaçăo de doses anuais de reforço. Rev. Saúde públ. (S. Paulo), 16: 144-148, 1982.
3. CHUTIVONGSE, S.; WILDE, H.; FIESBEIN, D.B.; BAER, G.M. & HEMACHUDAHT, T. - One-year study of the 2-1-1 instramuscular post-exposure rabies vaccine regimen in 100 severely exposure Thai patients using rabies immune globulin and VERO cell rabies vaccine. Vaccine, 9: 573-576, 1991.
4. FAVORETTO, S.R.; CARRIERI, M.L.; TINO, M.S. et al. Reduced schedule of human anti-rabies immunization with Fuenzalida & Palacios vaccine. Additional data. Rev. Inst. Med. trop. S. Paulo, 35: 281-284, 1993.
5. FAVORETTO, S.R.; CARRIERI, M.L.; TINO, M.S.; ZANETTI, C.R. & PEREIRA, O.A.C. - Simplified fluorescent inhibition microtest for the titration of rabies neutralizing antibodies. Rev. Inst. Med. trop. S. Paulo, 35: 171-175, 1993.
6. FUENZALIDA, E. & PALACIOS, R. - Un método mejorado en la preparación de la vacuna antirábica. Bol. Inst. bact. Chile, 8: 3-10, 1955.
7. HERZOG, M.; FRITZELL, C.; LAFAGE, M. et al. - T and B cell human response to European bat lyssavirus after post-exposure rabies vaccination. Clin. exp. Immunol., 85: 224-230, 1991.
8. KUWERT, E.K.; BARSENBACH, C.; WERNER, J. et al. - Early/high and late/ low responders among HDCS vaccines? In: KUWERT, E.; WIKTOR,T.J. & KOPROWSKI, H., ed. Cell culture rabies vaccines and their protective effect in man. Geneva, International Green Cross, p. 160.
9. LAFON, M.; BOURHY, H. & SUREAU, P. - Immunity against the European bat rabies (Duvenhage) virus induced by rabies vaccines: an experimental study in mice. Vaccine, 6: 362-368, 1988.
10. SELIGMAN Jr., E.B. - Prueba de potencia NIH. In: KAPLAN, M.M & KOPROWSKI, H. La Rabia: técnicas de laboratório. 3 ed. Ginebra, Organización Mundial de la Salud, 1976. p. 294-302. (Serie de Monografias, 23).
11. SINNECKER, H.; ATANASIU, P.; BAHMANYAR, M. et al. - Vaccine potency requirements for reduced immunization schedules and pre-exposure treatment. Develop. biol. Stand., 40: 268-270, 1978.
12. SUREAU, P.; ROLLIN, P.E.; FRITZELL, C.; TOUIR, M.Y. & LAFON, M. - A new reduced vaccination schedule for post-exposure treatment. Results obtained in France with commercially available cell culture vaccines. In: TONG-CHAOREN, P. & KURSTAR, E., ed. Virus diseases in Asia. Bangkok, Mahidol University. p.84.
13. VODOPIJA, I.; SUREAU, P. & LAFON, M. - An evaluation of second generation tissue culture rabies vaccines for use in man: a four vaccine comparative immunogenicity study using a pre-exposure vaccination schedule and an abbreviated 2-1-1 post-exposure schedule. Vaccine, 44: 245-248, 1986.
14. WORLD HEALTH ORGANIZATION - WHO expert committee on rabies; eight report. Wld. Hlth. Org. techn. Rep. Ser., (824), 1992.
15. ZANETTI, C.R.; CHAVES, L.B.; SILVA, A.C.R.; LEE, L.M. & PEREIRA, O.A.C. - Studies on human anti-rabies immunization in Brazil. I - Evaluation of the 3 + 1 pre-exposure vaccination schedule under field conditions. Rev. Inst. Med. trop. S. Paulo, 37(4), 1995.

Correspondence to:

Carlos Roberto Zanetti (PhD)

Instituto Pasteur

Av. Paulista, 393

01311-000 São Paulo, SP, Brazil

FAX: 55.11.289-0831

Publication Dates

Publication in this collection
21 Sept 2006
Date of issue
Aug 1995

History

Accepted
06 Apr 1995
Received
06 Feb 1995

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ALBAS, A.; MOURĂO FUCHES, R.M.; FRAZATTI GALLINA, N.M. et al. - Termoestabilidade da vacina contra raiva, tipo Fuenzalida & Palacios, uso humano. Rev. Inst. Med. trop. S.Paulo, 34: 27-31, 1992.

[2] 2. CHAMELET, E.L.B.; AZEVEDO, M.P.; FAVORETTO, S.R.; KERBRIE, S.V. & SOUZA, L.T.M. - Esquema reduzido de vacinaçăo anti-rábica humana pré-exposiçăo e avaliaçăo de doses anuais de reforço. Rev. Saúde públ. (S. Paulo), 16: 144-148, 1982.

[3] 3. CHUTIVONGSE, S.; WILDE, H.; FIESBEIN, D.B.; BAER, G.M. & HEMACHUDAHT, T. - One-year study of the 2-1-1 instramuscular post-exposure rabies vaccine regimen in 100 severely exposure Thai patients using rabies immune globulin and VERO cell rabies vaccine. Vaccine, 9: 573-576, 1991.

[4] 4. FAVORETTO, S.R.; CARRIERI, M.L.; TINO, M.S. et al. Reduced schedule of human anti-rabies immunization with Fuenzalida & Palacios vaccine. Additional data. Rev. Inst. Med. trop. S. Paulo, 35: 281-284, 1993.

[5] 5. FAVORETTO, S.R.; CARRIERI, M.L.; TINO, M.S.; ZANETTI, C.R. & PEREIRA, O.A.C. - Simplified fluorescent inhibition microtest for the titration of rabies neutralizing antibodies. Rev. Inst. Med. trop. S. Paulo, 35: 171-175, 1993.

[6] 6. FUENZALIDA, E. & PALACIOS, R. - Un método mejorado en la preparación de la vacuna antirábica. Bol. Inst. bact. Chile, 8: 3-10, 1955.

[7] 7. HERZOG, M.; FRITZELL, C.; LAFAGE, M. et al. - T and B cell human response to European bat lyssavirus after post-exposure rabies vaccination. Clin. exp. Immunol., 85: 224-230, 1991.

[8] 8. KUWERT, E.K.; BARSENBACH, C.; WERNER, J. et al. - Early/high and late/ low responders among HDCS vaccines? In: KUWERT, E.; WIKTOR,T.J. & KOPROWSKI, H., ed. Cell culture rabies vaccines and their protective effect in man. Geneva, International Green Cross, p. 160.

[9] 9. LAFON, M.; BOURHY, H. & SUREAU, P. - Immunity against the European bat rabies (Duvenhage) virus induced by rabies vaccines: an experimental study in mice. Vaccine, 6: 362-368, 1988.

[10] 10. SELIGMAN Jr., E.B. - Prueba de potencia NIH. In: KAPLAN, M.M & KOPROWSKI, H. La Rabia: técnicas de laboratório. 3 ed. Ginebra, Organización Mundial de la Salud, 1976. p. 294-302. (Serie de Monografias, 23).

[11] 11. SINNECKER, H.; ATANASIU, P.; BAHMANYAR, M. et al. - Vaccine potency requirements for reduced immunization schedules and pre-exposure treatment. Develop. biol. Stand., 40: 268-270, 1978.

[12] 12. SUREAU, P.; ROLLIN, P.E.; FRITZELL, C.; TOUIR, M.Y. & LAFON, M. - A new reduced vaccination schedule for post-exposure treatment. Results obtained in France with commercially available cell culture vaccines. In: TONG-CHAOREN, P. & KURSTAR, E., ed. Virus diseases in Asia. Bangkok, Mahidol University. p.84.

[13] 13. VODOPIJA, I.; SUREAU, P. & LAFON, M. - An evaluation of second generation tissue culture rabies vaccines for use in man: a four vaccine comparative immunogenicity study using a pre-exposure vaccination schedule and an abbreviated 2-1-1 post-exposure schedule. Vaccine, 44: 245-248, 1986.

[14] 14. WORLD HEALTH ORGANIZATION - WHO expert committee on rabies; eight report. Wld. Hlth. Org. techn. Rep. Ser., (824), 1992.

[15] 15. ZANETTI, C.R.; CHAVES, L.B.; SILVA, A.C.R.; LEE, L.M. & PEREIRA, O.A.C. - Studies on human anti-rabies immunization in Brazil. I - Evaluation of the 3 + 1 pre-exposure vaccination schedule under field conditions. Rev. Inst. Med. trop. S. Paulo, 37(4), 1995.

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