Cross-protection correlates with delayed antibody formation to challenge virus after immunization with Sindbis virus

Mice immunized with Sindbis virus, strains HR (heat-resistant) or AR339, by a dual injection given intracerebrally (i.c.) and intraperitoneally (i.p.) at day zero, were cross-protected from challenge at day 10 with Semliki Forest virus (SFV). Neutralizing and haemagglutination-inhibition antibodies to Sindbis are detected in high titre by day 6 after immunization but no cross-reacting antibodies to SFV were found up to day 42. Immunized mice that were challenged with SFV showed an 8 to 10 day delay in the appearance of antibody to SFV compared to mice that were sham-inoculated. Thus, cross-protection in Sindbis-immunized animals was correlated with a temporary suppression of antibody formation to the challenge virus (SFV), while the appearance of high titre antibody to SFV in sham-immunized mice after challenge with SFV did not protect.