Comparison of the immune responses induced by chimeric alphavirus-vectored and formalin-inactivated alum-precipitated measles vaccines in mice.
A variety of vaccine platforms are under study for development of new vaccines for measles. Problems with past measles vaccines are incompletely understood and underscore the need to understand the types of immune responses induced by different types of vaccines. Detailed immune response evaluation is most easily performed in mice. Although mice are not susceptible to infection with wild type or vaccine strains of measles virus, they can be used for comparative evaluation of the immune responses to measles vaccines of other types. In this study we compared the immune responses in mice to a new protective alphavirus replicon particle vaccine expressing the measles virus hemagglutinin (VEE/SIN-H) with a non-protective formalin-inactivated, alum-precipitated measles vaccine (FI-MV). MV-specific IgG levels were similar, but VEE/SIN-H antibody was high avidity IgG2a with neutralizing activity while FI-MV antibody was low-avidity IgG1 without neutralizing activity. FI-MV antibody was primarily against the nucleoprotein with no priming to H. Germinal centers appeared, peaked and resolved later for FI-MV. Lymph node MV antibody-secreting cells were more numerous after FI-MV than VEE/SIN-H, but were similar in the bone marrow. VEE/SIN-H-induced T cells produced IFN-gamma and IL-4 both spontaneously ex vivo and after stimulation, while FI-MV-induced T cells produced IL-4 only after stimulation. In summary, VEE/SIN-H induced a balanced T cell response and high avidity neutralizing IgG2a while FI-MV induced a type 2 T cell response, abundant plasmablasts, late germinal centers and low avidity non-neutralizing IgG1 against the nucleoprotein.
Bergen
M Jeff
MJ
Graduate Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Pan
Chien-Hsiung
CH
Greer
Catherine E
CE
Legg
Harold S
HS
Polo
John M
JM
Griffin
Diane E
DE
D000524:Alphavirus / Q000235:genetics; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D000915:Antibody Affinity; D005557:Formaldehyde / Q000494:pharmacology; D005822:Genetic Vectors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006388:Hemagglutinins / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D008458:Measles Vaccine / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000534:Alum Compounds; D006388:Hemagglutinins; D007074:Immunoglobulin G; D008458:Measles Vaccine; D019444:Vaccines, DNA; D015164:Vaccines, Inactivated; D005557:Formaldehyde