title: The smallpox vaccine induces an early neutralizing IgM response.
abstract: The antibody response elicited after immunization with vaccinia virus (VacV) is known to be sufficient to confer host protection against VacV or smallpox. In humans it has been shown that such anti-VacV antibody production can be sustained for decades. Nevertheless, little is known about the kinetics and the role in protection of the early antibody response after vaccination. In this study we identify VacV neutralizing IgM antibodies as early as 4 days after infection of C57BL/6 mice. Most of this IgM production is T cell dependent and predominantly independent of the germinal center reaction (SAP/SH2D1A independent). Importantly, the IgM neutralized both infectious forms of VacV: the intracellular mature virion (MV, IMV) and the extracellular enveloped virion (EV, EEV). Moreover, in mice primed with MHCII restricted peptides, an increase in the total VacV neutralizing antibody titers was seen, a large component of which was neutralizing IgM against the same protein from which the priming peptide was derived. To further demonstrate the biological relevance of this early neutralizing response, we examined anti-VacV antibodies in humans after vaccination. Human subjects could be divided into two groups early after immunization: IgG(hi) and IgG(lo). VacV IgM neutralizing antibodies were detected in the IgG(lo) group. Taken together these results indicate that both in a small animal model and in humans an early neutralizing IgM response after VacV immunization is present and likely contributes to control of the infection prior to the development of a robust IgG response.
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Moyron-Quiroz
authors.forename: Megan M
authors.initials: MM
authors.lastname: McCausland
authors.forename: Robin
authors.initials: R
authors.lastname: Kageyama
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: Shane
authors.initials: S
authors.lastname: Crotty
mesh_terms: D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood* / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002522:Chlorocebus aethiops; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009500:Neutralization Tests; D040081:Protein Array Analysis; D012899:Smallpox / Q000276:immunology / Q000517:prevention & control*; D012900:Smallpox Vaccine / Q000276:immunology*; D014709:Vero Cells; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012900:Smallpox Vaccine