Reductions in cross-neutralizing antibody responses in infants after attenuation of the human rotavirus vaccine candidate 89-12

Abstract

The G1P1A[8] rotavirus vaccine candidate 89-12, the precursor to Rotarix, stimulated high titers of neutralizing antibodies to non-G1/P1A[8] serotypes of human rotavirus in naturally infected subjects before attenuation by cell-culture passages. These responses were greatly diminished in young infants (median age, 11 weeks) administered the attenuated vaccine. Because of the possibility of improved responses in older infants, the immunogenicity of the 89-12 vaccine candidate was evaluated after administration of 2 doses beginning at either 4 or 6 months of age. As was found in young infants, neutralizing antibody responses to non-G1/P1A[8] rotaviruses were considerably lower than those observed after natural infection. The reasons identified were overall (P<.0001) lower neutralizing antibody responses stimulated by the attenuated 89-12 strain, compared with those stimulated by its virulent precursor, and 5 mutations selected in the gene encoding the immunodominant VP4 (P) neutralization protein. Even so, the Rotarix vaccine developed from attenuated 89-12 was found to elicit excellent protection against non-G1 rotaviruses.