Inactivated rotavirus vaccine induces protective immunity in gnotobiotic piglets.
Live oral rotavirus vaccines that are effective in middle and high income countries have been much less immunogenic and effective among infants in resource-limited settings. Several hypotheses might explain this difference, including neutralization of the vaccine by high levels of maternal antibody in serum and breast milk, severe malnutrition, and interference by other flora and viruses in the gut. We have pursued development of an alternative parenteral rotavirus vaccine with the goal of inducing comparable levels of immunogenicity and efficacy in populations throughout the world regardless of their income levels. In the present study, we assessed the immunogenicity and protection of a candidate inactivated rotavirus vaccine (IRV), the human strain CDC-9 (G1P[8]) formulated with aluminum phosphate, against rotavirus infection in gnotobiotic piglets. Three doses of IRV induced high titers of rotavirus-specific IgG and neutralizing activity in the sera of gnotobiotic piglets and protection against shedding of rotavirus antigen following oral challenge with a homologous virulent human strain Wa (G1P[8]). Our findings demonstrate the proof of concept for an IRV in a large animal model and provide evidence and justification for further clinical development as an alternative candidate vaccine.
Wang
Yuhuan
Y
Division of Viral Diseases, Centers for Diseases Control and Prevention, Atlanta, GA, USA.
Azevedo
Marli
M
Saif
Linda J
LJ
Gentsch
Jon R
JR
Glass
Roger I
RI
Jiang
Baoming
B
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000276:immunology; D008895:Milk, Human / Q000276:immunology; D011247:Pregnancy; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000276:immunology / Q000494:pharmacology*; D013552:Swine; D015164:Vaccines, Inactivated / Q000276:immunology / Q000494:pharmacology
D000914:Antibodies, Viral; D022243:Rotavirus Vaccines; D015164:Vaccines, Inactivated