LCMV nAbs Arise Preferentially in Chronic Infection and Require Somatic Hypermutation
(A–C) We infected mice with rCl13 or rARM and measured viremia (A), GP1-binding IgG titers (B), and virus-neutralizing antibodies (C) from blood on the indicated days. Symbols and bars represent means ± SEM in (A), (B), and (C, left panel). The right panel in (C) shows nAb titers of individual animals on day 62. Number of biological replicates (n) = 3–15 (A), n = 5 (B), n = 12–15 (C). Number of independent experiments (N) = 3. Two-way ANOVA with Bonferroni’s post-test for multiple comparisons. ∗∗p < 0.01.
(D and E) Binding of the rCl13-neutralizing antibodies WEN-1 and WEN-3, of their respective unmutated ancestors WEN-1UA and WEN-3UA and of an irrelevant isotype control antibody to WE-GP (D). Ability of the indicated antibodies to neutralize rCl13 (E). Symbols show the means of two technical replicates. N = 2.
(F) We infected mice with rCl13 on day 0, followed by passive immunization with the indicated antibodies on day 3. Viremia was monitored. Symbols represent the means ± SEM of three to four mice (WEN-1, one representative experiment) and of four to six mice (WEN-3, two combined experiments), respectively. N = 2. See also Figure S1.