Print version ISSN 0036-4665
Rev. Inst. Med. trop. S. Paulo vol.50 no.2 São Paulo Mar./Apr. 2008
Soroconversão à vacina contra hepatite B após redução de peso em obeso não respondedor
Maria Isabel Saraiva Dinelli; Maria Isabel de Moraes-Pinto
Department of Pediatrics, Division of Pediatric Infectious Diseases, Federal University of São Paulo, São Paulo, SP, Brazil
Decreased responses to hepatitis B vaccine have been associated with some host conditions including obesity. Susceptible non-responders to a primary three-dose vaccine series should be revaccinated. Those who maintain a non-responder condition after revaccination with three vaccine doses are unlikely to develop protection using more doses. This is a description of an obese woman who received six doses of hepatitis B vaccine and persisted as a non-responder. She was submitted to a vertical banded gastroplasty Roux-en-Y gastric bypass Capellas's technique. After weight reduction, she received three additional doses of vaccine and seroconverted. Further studies should help clarify the need to evaluate antibody levels and eventually revaccinate the increasing population of individuals who undergo weight reduction.
Keywords: Hepatitis B; Vaccine; Non-responder; Obesity; Gastroplasty.
A diminuição da resposta à vacinação contra hepatite B já foi relacionada a algumas condições clínicas, inclusive à obesidade. Indivíduos que não responderam à série de três doses devem ser revacinados. Caso continuem não-respondedores após duas séries de vacina, não há indicação de doses adicionais. Esta é a descrição de mulher obesa que não havia soroconvertido após ter recebido seis doses de vacina contra hepatite B. Ela foi submetida à gastroplastia em Y de Roux, pela técnica de Capella. Após a redução de peso, a paciente recebeu mais três doses de vacina contra hepatite B e soroconverteu. Novos estudos poderão indicar a necessidade de avaliação de níveis de anticorpos contra antígenos vacinais e eventualmente revacinar esta população cada vez maior de pacientes que se submetem à cirurgia para redução de peso.
Hepatitis B vaccine is highly immunogenic. Three vaccine doses induce protective antibodies (anti-HBs > 10 mIU/mL) in over 90% of healthy adults under 40 years of age3,10,12. Response to vaccination in children and adolescents occurs in more than 95% of vaccinees10. Decreased vaccine responses have been associated with some host conditions, such as older age, male gender, smoking, genetic factors, chronic disease, and obesity2-3,8,10-12,14,16-19. Also, poor antibody response in obese persons may be linked to inadvertent injection of vaccine into adipose tissue16.
Individuals who do not attain anti-HBs > 10 mIU/mL after a primary vaccine series should be revaccinated. Those who maintain a non-responder condition after revaccination with three vaccine doses are unlikely to develop protection using further doses3,10. A variable seroconversion rate was achieved after revaccination in different studies3-5,20-21. Higher body mass index was associated to lower geometric mean titres (GMTs) after a revaccination series4.
This is a description of an obese 31-year-old woman, previously susceptible to hepatitis B infection (with negative anti-HBs and anti-HBc antibodies). Her body mass index, weight (kg) / height (m)2, was 37.3% during the first 3-dose vaccination schedule (0, 1 and 8 months) and 35.7% in the second 3-dose schedule (0, 1, 6 months). Hepatitis B recombinant DNA vaccines were from SmithKlein Beecham Biologicals (Rixensart, Belgium), but for the sixth dose, which was from Merck Sharp Dohme (West Point, USA). All doses were injected intramuscularly into the deltoid muscle. After six vaccine doses, the patient was a non-responder, with negative anti-HBs, anti-HBc and HBs-Ag as assessed by radioimmunoassay (Abbott, USA). Nine months after the last vaccine dose, the patient was submitted to a laparoscopic vertical banded gastroplasty Roux-en-Y gastric bypass, Capellas's technique. She lost weight, and her body mass index dropped to 20.5%. At that time point, she was re-tested for anti-HBs antibodies by electrochemiluminescence assay (Roche) and was not reagent. Although there were no recommendations for revaccination among healthy adults who did not seroconvert after two vaccine series, the patient received a third series of vaccines against hepatitis B from Merck Sharp Dohme (West Point, USA) in a 0, 1, 6 month schedule again in the deltoid muscle. Three months after the third dose, anti-HBs antibody concentration increased to 39 mUI/mL as assessed by electrochemiluminescence (Roche).
Obesity has been associated with many health conditions, such as coronary heart disease, hypertension, diabetes mellitus and dyslipidemia. Obese individuals can also have dysfunction in the immune system7,9,15. Previous studies have shown an association between obesity and poor antibody response to hepatitis B vaccine2-3,12,14,16,18. Different studies have shown that lymphocytes from obese individuals have altered number and also a reduced lymphoproliferative response to "in vitro" stimuli7,9,15. TANAKA et al. noted that obese subjects had diminished number of CD3+, CD4+ and CD8+ T cells and a reduced blastogenic T cell response to mitogens. Interestingly, weight reduction led to an increase in T cell responses and in the number of CD4+ and NK cells15.
On the other hand, it is known that individuals who do not present a serologic response to hepatitis B vaccine can develop a specific cellular immune response6. Also, non-responder individuals to the current licensed hepatitis B vaccine might benefit from new candidate vaccines with different antigens and adjuvants5,13,22.
As our patient responded to the extra three-dose vaccine scheme after weight reduction, factors such as an altered immune response due to obesity or inadverted injection of previous vaccine doses into adipose tissue might have been responsible for the lack of seroconvertion after two vaccine series. Further studies should help clarify the need to evaluate antibody levels and eventually revaccinate the increasing population of individuals who undergo surgery for weight reduction.
1. AMERICAN ACADEMY OF PEDIATRICS - Red Book. Report of the Committee on Infectious Diseases, Pickering, L.K., ed. 27. ed. Elk Grove Village, American Academy of Pediatrics, 2006. [ Links ]
2. ASSAD, S. & FRANCIS, A. - Over a decade of experience with a yeast recombinant hepatitis B vaccine. Vaccine, 18: 57-67, 1999. [ Links ]
3. AVERHOFF, F.; MAHONEY, F.; COLEMAN, P. et al. - Immunogenicity of hepatitis B vaccines implications for persons at occupational risk of hepatitis B virus infection. Amer. J. prevent. Med., 15: 1-8, 1998. [ Links ]
4. CLEMENS, R.; SÄNGER, R.; KRUPPENBACHER, J. et al. - Booster immunization of low and non-responders after standard three dose hepatitis B vaccine schedule - results of a post-marketing surveillance. Vaccine, 15: 349-352, 1997. [ Links ]
5. JACQUES, P.; MOENS, G.; DESOMBERE, I. et al. - The immunogenicity and reatogenicity profile of a candidate hepatitis B vaccine in adult vaccine non-responder population. Vaccine, 20: 3644-3649, 2002. [ Links ]
6. JARROSSON, I.; KOLOPP-SARDA, M.N.; AGUILAR, P. et al. - Most humoral non-responders to hepatitis B vaccines develop HBV-specific cellular immune responses. Vaccine, 22: 3789-3796, 2004. [ Links ]
7. LAMAS, O.; MARTI, A. & MARTINEZ, J.A. - Obesity and immunocompetence. Europ. J. clin. Nutr., 56: 542-545, 2002. [ Links ]
8. LOUTHER, J.; FELDMAN, J.; RIVERA, P. et al. - Hepatitis B vaccination program at a New York City hospital: seroprevalence, seroconversion and declination. Amer. J. Infect. Control, 26: 423-427, 1998. [ Links ]
9. MARTI, A.; MARCOS, A. & MARTINEZ, J.A. - Obesity and immune function relationships. Obesity Rev., 2: 131-140, 2001. [ Links ]
10. MAST, E.E.; MARGOLIS, H.S.; FIORE, A.E. et al. - A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. M.M.W.R., 54(RR16): 1-23, 2005. [ Links ]
11. RENDI-WAGNER, P.; KUNDI, M.; STEMBERGER, H. et al. - Antibody-response to three recombinant hepatitis B vaccines: comparative evaluation of multicenter travel-clinic based experience. Vaccine, 19: 2055-2060, 2001. [ Links ]
12. ROOME, A.J.; WALSH, S.J.; CARTTER, M.L. & HADLER, J.L. - Hepatitis B vaccine responsiveness in Connecticut public safety personnel. J. Amer. med. Ass., 270: 2931-2934, 1993. [ Links ]
13. ROTTINGHAUS, S.T.; POLAND, G.A.; JACOBSON, R.M.; BARR, L.J. & ROY, M.J. - Hepatitis B DNA vaccine induces protective antibody responses in human non-responders to conventional vaccination. Vaccine, 21: 4604-4608, 2003. [ Links ]
14. SIMÓ-Miñana, J.; GAZTAMBIDE-Ganuza, M.; FERNANDEZ-Millan, P. & PEÑA-Fernandez, M. - Hepatitis B vaccine immunoresponsiveness in adolescents: a revaccination proposal after primary vaccination. Vaccine, 14: 103-106, 1996. [ Links ]
15. TANAKA, S.I.; ISODA, F.; ISHIHARA, Y.; KIMURA, M. & YAMAKAWA, T. - T lymphopaenia in relation to body mass index and TNF-a in human obesity: adequate weight reduction can be corrective. Clin. Endocr., 54: 347-354, 2001. [ Links ]
16. WEBER, D.J.; RUTALA, W.A.; SAMSA, P.; SANTIMAW, J.E. & LEMON, M. - Obesity as a predictor of poor antibody response to hepatitis B plasma vaccine. J. Amer. med. Ass., 254: 3187-3189, 1985. [ Links ]
17. WINTER, A.P.; FOLLETT, E.A.C.; MCINTYRE, J.; STEWART, J. & SYMINGTON, I.S. - Influence of smoking on immunological response to hepatitis B vaccine. Vaccine, 12: 771-772, 1994. [ Links ]
18. WOOD, R.C.; MACDONALD, K.L.; WHITE, K.E. et al. - Risk factors for lack antibody following hepatitis B vaccination of Minnesota health care workers. J. Amer. med. Ass., 270: 2935-2939, 1993. [ Links ]
19. YEN, Y.H.; CHEN, C.H.; WANG, J.H. et al. - Study of hepatitis B (HB) vaccine non-responsiveness among health care workers from an endemic area (Taiwan). Liver Int., 25: 1162-1168, 2005. [ Links ]
20. ZANETTI, A.R.; MARIANO, A.; ROMANÒ, L. et al. - Long-term immungenicity of hepatitis B vaccination and policy for booster: an Italian multicentre study. Lancet, 366: 1379-1384, 2005. [ Links ]
21. ZHUANG, G.H.; YAN, H.; WANG, X.L. et al. - Hepatitis B revaccination in healthy non-responder Chinese children: five-year follow-up of immune response and immunologic memory. Vaccine, 24: 2186-2192, 2006. [ Links ]
22. ZUCKERMAN, J.N.; SABIN, C.; CRAIG, F.M.; WILLIAMS, A. & ZUCKERMAN, A.J. - Immune response to a new hepatitis B vaccine in healthcare workers who had not responded to standard vaccine: randomised double blind dose-response study. B.M.J., 314: 329, 1997. [ Links ]
Maria Isabel Saraiva Dinelli
Rua Pedro de Toledo 781, 9º andar
04039-032 São Paulo, SP, Brasil
Phone: +55 11 5574.6471, Fax: +55 11 5575.6928
Received: 7 May 2007
Accepted: 27 November 2007