Could exposure to anti-D immunoglobulin (Rhesonativ) attenuate the prophylactic effect of influenza

Fråga: Could exposure to anti-D immunoglobulin (Rhesonativ) attenuate the prophylactic effect of influenza vaccine (Pandemrix)?

In Fass, it is mentioned that live attenuated virus vaccines should not be administered within three months after treatment with Rhesonativ, since this could impede the immune response.

Sammanfattning: There is no empiric evidence of a clinically relevant interaction between immunoglobulins and vaccines other than attenuated virus strains. However, exogenous antibodies directed against vaccine antigens could theoretically attenuate the immune response to other kinds of vaccines as well. In the present case, the administered immunoglobulins are unlikely to include antibodies directed against the A(H1N1) influenza strain and no interaction is to be expected.

Svar: Rhesonativ is primarily used to prevent immunisation against the erythrocyte D (Rh)-antigen in Rh-negative women giving birth to a potentially Rh-positive child. According to the summary of products characteristics (SPC) Rhesonativ contains specific IgG antibodies against the D (Rh)-antigen (1). However, it is manufactured by harvesting IgG antibodies from Rh-negative volunteers after immunising them by exposure to the D antigen. Although the recent immunisation should result in a high concentration of anti-D antibodies, the drug is not strictly selective and it does indeed expose the Rhesonativ-treated woman to antibodies against all the antigens to which the volunteers have previously been immunised (2).

When live virus vaccines are used for immunisation, the antigens present in the administered dose are not sufficient for an adequate immune response. Rather, the immunisation requires continuous replication of the attenuated virus to produce sufficient amounts of the antigen (3). Administration of neutralizing antibodies directed against the virus vaccine strain prior to vaccination could attenuate the immune response by inhibiting virus replication, and reduced effectiveness of rubella and measles vaccines have been demonstrated several months after administration of immunoglobulins (4).

The influenza vaccine consists of split, inactivated influenza virus. Thus, it is not a live virus vaccine and the warning against using such vaccines after administration of Rhesonativ is not formally applicable (1, 5). If antibodies directed against the influenza virus are administered together with the anti-D immunoglobulin, this could theoretically inactivate some of the influenza antigens in the vaccine but according to the manufacturer of Rhesonativ this is unlikely to compromise the effectiveness of the vaccine (2). However, a clinical immunologist specialising in vaccines and immune defects comes to the opposite conclusion and suggests that inactivated vaccines could theoretically be more prone to inactivation by circulating antibodies than the attenuated virus strains. The reason for this would be that the live vaccines, unlike the inactivated ones, are rapidly transferred into the cells for replication, where they are inaccessible to circulating antibodies (6).

Regardless of whether or not treatment with immunoglobulins can interact with vaccines other than the live ones, this is probably not applicable to the combination Rhesonativ-Pandemrix, since the individuals from whom the Rhesomativ immunoglobulins originate were unlikely to be immunized against the A(H1N1) influenza at the time the antibodies were harvested (6). FASS 2009 Personal communication with Linnea Källgren, Octapharma AB, Stockholm, Sweden (2009-11-06) Bukreyev A, Belyakov IM. Expression of immunomodulating molecules by recombinant viruses: can the immunogenicity of live virus vaccines be improved? Expert Rev Vaccines 2002;1(2):233-245 Interference of immune globulin with measles and rubella immunization. (No authors listed). Eur J Pediatr 1993;152(6):536 Pandemrix suspension. SPC, GlaxoSmithKline (2009-11-11) Personal communication with prof. Lennart Hammarström, Div. of Clinical Immunology, Karolinska University Hospital Huddinge, Stockholm, Sweden (2009-11-16)