Transfer of Anti-Rotavirus Antibodies during Pregnancy and in Milk Following Maternal Vaccination with a Herpes Simplex Virus Type-1 Amplicon Vector

Meier, Anita F.; Suter, Mark; Schraner, Elisabeth M.; Humbel, Bruno M.; Tobler, Kurt; Ackermann, Mathias; Laimbacher, Andrea S.

Having the same antigens (VP2, VP6, and VP7) included in our approach and having shown that all three proteins were being synthesized in transduced cells, we were confident to achieve similar results in a protection study as Coste et al. [27] , though with IgG and upon in situ synthesis of the viral proteins instead of immunizing with purified VLPs. Indeed, our vaccinated mice produced high anti RV IgG antibody titers, both in serum and in milk, and they transferred these antibodies to their offspring. However, we were unable to detect any RV specific IgA antibodies in the vaccinated mice. Consequently, a clear protection against diarrhea was not achieved. This was in agreement with previous studies [34, 36] , which reported that protection from rotavirus diarrhea relied on the lactogenic transfer of IgA against VP7 or VP4. Of course, several factors contribute to clinical protection against RV, including a close match of antibodies against the targeted antigens, the amount and isotype of antibodies as well as the location, where they should act. In the present case, the transfer of antibodies from the immunized mothers to their suckling mice seemed efficient. However, at least three factors might have influenced the protective outcome in a negative way: (1) The stringent stop criteria for the animal experiments did not allow the examination of the duration and severity of RV symptoms in offspring in the different experimental groups; (2) The antibody isotype generated upon vaccination was predominantly IgG, whereas IgA is supposed to provide a better level of protection, particularly in the gut. On the other hand, one may consider that the maternal antibodies had been recovered from the gut as a consequence of suckling milk containing these antibodies. Thus, the challenging virus and the potentially protective antibodies had opportunities to meet and to react in the gut, at least for a certain amount of time. It was, therefore, surprising to note that no obvious protective effect could be achieved. Of note, we used heterologous RVLPs based on the human RV strain Wa and mice were challenged with a heterotypic RV, the murine strain EDIM. Thus, it might be that even if VP7-specific antibodies were raised, no protection was observed because of the poor cross-reactivity between the raised antibodies; (3) According to Butler et al. [21] , the mammals cluster into three groups, with respect to lactogenic immunity. Rodents, classified in group 2, show particularly good absorption of IgG from the gut, which drains the gut from functional antibodies. Humans, classified in group 1, absorb only little immunoglobulins from the gut, leaving the antibodies to work where they are supposed to throughout a RV infection. Pigs, classified in group 3, show extensive absorption of all classes of immunoglobulins but only for the first 12 h. Afterwards, the milk antibodies are known to work for several weeks particularly well in the porcine gut. This property is even enhanced by the ability of the pigs to produce high amounts of IgA in response to vaccination.