• Can a different brand of hepatitis A be used to complete a primary course?
• Does a course of hepatitis A vaccine need to be repeated if there has been a long interval between the first and second doses?
• Is there a need for doses of hepatitis A vaccines after the two dose schedule has been completed?

Q. Can a different brand of hepatitis A be used to complete a primary course?

A.   Yes. Any current brand of hepatitis A vaccine can be used to boost another.

It is good practice to use the same brand of vaccine to complete a course. However, there may be occasions when this is not possible.

All hepatitis A vaccines are made from whole hepatitis A virus propagated in human diploid cells, although the final formulations of the vaccines differ.

Epaxal has been demonstrated to boost Havrix [1] and studies indicate that Havrix, Avaxim and Vaqta are interchangeable [2,3,4].

The SPC for Epaxal was amended in January 2005 to state that it can be used interchangeably with other inactivated hepatitis A vaccines for the first and second dose. (5)

References:

1. Beck BR, Hatz CFR, Loutan L, Steffen R. Immunogenicity of booster hepatitis A vaccine after primary immunization with an aluminium-adsorbed hepatitis A vaccine. J Travel Med 2004; 11:201-207

2. Sanofi Pasteur MSD and GlaxoSmithKline: Summary of Product Characteristics for Avaxim, Vaqta Paediatric and Havrix.

3. Clarke P, Kitchin N, Souverbie F. A randomised comparison of two inactivated hepatitis A vaccines, Avaxim and Vaqta, given as a booster to subjects primed with Avaxim. Vaccine. 2001; 19: 4429-4433

4. Zuckerman JN, Kirkpatrick CT , Huang M. Immunogenicity and reactogenicity of Avaxim (160 AU) as compared with Havrix (1440 EL.U) as a booster following primary immunization with Havrix (1440EL.U) against hepatitis A. J Travel Med. 1998; 5: 18 -22

5. Instituto Sieroterapico Berna s.r.l. Summary of Product Characteristics for Epaxal. Revised 5 January 2005

 

Q. Does a course of hepatitis A vaccine need to be repeated if there has been a long interval between the first and second doses?

A.   No. A primary course of hepatitis A vaccine does not need to be repeated.

An excellent immune response is obtained after a single dose of hepatitis A vaccine. In order to induce long-term immunity and protection, a second (booster) dose of vaccine should be given. The Summary of Product Characteristics (SPC) for all hepatitis A vaccines state that this second dose should optimally be given 6 to 12 months following the first dose of vaccine.

The SPC for Avaxim states that the second dose may be administered up to 36 months following the first [1].

The SPC for Havrix Monodose states that if the second, booster dose of vaccine is delayed up to 3 years after the primary dose, antibody levels are produced that are similar to those following a booster dose administered within the recommended time interval [2].

The SPC for Epaxal states that the second dose may be given up to 4 years following the first dose, based on experience in adult travellers [3].

Although booster doses delayed beyond the recommended intervals described above are not covered by the product licence, research indicates that a second dose given at long intervals will still result in a boosting immune response [4, 5, 6, 7]. A second dose of Havrix given up to 8 years after the first dose boosted the primary dose [4, 6]. Good protective antibody levels have also been achieved when the second dose of Epaxal was given up to 56 months after the primary dose [5].

Thus, based on evidence from available studies, there is no interval which would require restarting a course of hepatitis A vaccine.

References:

1. Sanofi Pasteur MSD. Summary of Product Characteristics for Avaxim, revised June 2004.

2. GlaxoSmithKline. Summary of Product Characteristics for Havrix Monodose, revised 25 June 2002 .

3. Instituto Sieroterapico Berna s.r.l. Summary of Product Characteristics for Epaxal. Revised 5 January 2005 .

4. Landry P, Tremblay S, Darioli R, Genton B. Inactivated hepatitis A vaccine booster given >/= 24 months after primary dose. Vaccine. 2001; 19: 399-402.

5. Beck B, Hatz C, Broennimann R et al. Immunogenicity of two doses of a virosome formulated hepatitis A vaccine administered 18 to 56 months apart (abstract) Clin Microbiolo Infect. 2000; 6 (suppl 10:We07).

6. Iwarson S, Lindh M and Widerstrom L. Excellent booster response 4 to 8 years after a single primary dose of an inactivated hepatitis A vaccine. J Travel Med 2004;11:120-121.

7. Van Damme P, Banatvala J, Fay O, et al. Hepatitis A booster vaccination: is there a need? Lancet 2003;362:1065-1071.

 

Q. Is there a need for doses of hepatitis A vaccines after the two dose schedule has been completed?

A. Not at the present. A 20 year duration of protection has been accepted by the Joint Committee on Vaccination and Immunisation, however, protection may be lifelong following 2 doses of vaccine in immunologically normal hosts.

The SPC for Avaxim states that the booster dose of hepatitis A vaccine will elicit protective antibodies that are expected to persist for at least 10 years [1].

The SPC for Havrix Monodose states that at least 97% of subjects will remain seropositive 25 years after vaccination [2].

The SPC for Epaxal states that mathematical models suggest that protection will persist for at least 20 years in the majority of vaccinees [3].

Anti-hepatitis A antibodies, which are considered a marker for protection against hepatitis A, have been demonstrated for up to 12 years in adults and 5 years in children [4, 5]. Different mathematical models based on different vaccine products have consistently predicted titres to last for > 20 years [6] Some have predicted antibody persistence up to 55 years [7].

It can also be expected that exposure to hepatitis A virus will induce an anamnestic protective response following a primary course of hepatitis A vaccine.

In summary, there is no need to provide a booster dose of vaccine following a primary series of hepatitis A vaccine in immune competent children and adults. The duration of protection from the primary series can be expected to be at least 20 years and probably indefinite.

References:

1. Sanofi Pasteur MSD. Summary of Product Characteristics for Avaxim, revised June 2004

2. GlaxoSmithKline. Summary of Product Characteristics for Havrix Monodose, revised 5 April 2006

3. Instituto Sieroterapico Berna s.r.l. Summary of Product Characteristics for Epaxal. Revised 5 January 2005 .

4. 1. Van Herck K, Van Damme P, Lievens M and Stoffel M. Hepatitis A vaccine: indirect evidence of immune memory 12 years after the primary course. J Med Virol 2004;72:194-196.

5. 1. Fan PC, Chang MH, Lee PI, et al. Follow-up immunogenicity of an inactivated hepatitis A virus vaccine in healthy children: results after 5 years. Vaccine 1998;16:232-235.

6. Van Damme P, Banatvala J, Fay O et al. Hepatitis A booster vaccination: is there a need? Lancet. 2003; 362: 1065-1071

7. Bovier PA, Bock J, Loutan L et al. Long-term immunogenicity of an inactivated virosome hepatitis A vaccine. J Med Virol. 2002;68:489-93.