The Anamnestic Antibody Response to Japanese Encephalitis Virus in Monkeys and its Implications Concerning Naturally Acquired Immunity in Man

Abstract

Summary Primary and anamnestic antibody responses to infectious Japanese encephalitis (JE) virus were studied in monkeys. The intradermal anamnestic dose of virus in suspensions of Japanese mosquitoes collected in nature was small, essentially equal to the intradermal infectious dose for susceptible monkeys, and well within the range of virus which vector mosquitoes might inoculate. Anamnestic antibody responses were uniformly measurable by hemagglutination-inhibition (HI) tests, usually detectable by complement fixation (CF) tests, but only infrequently demonstrable by virus-dilution neutralization tests. That anamnestic antibody responses resulted merely from virus antigen inoculated intradermally and did not depend on multiplication of virus in blood, skin or superficial tissues of previously infected monkeys was evidenced by a) lack of measurable viremia and virus proliferation in skin or superficial tissues and b) the ability of noninfectious, ultraviolet-irradiated virus to stimulate anamnestic antibody responses as readily as infectious virus. The fact that small amounts of infectious virus stimulated anamnestic antibody responses in previously infected, nonviremic monkeys, whereas large amounts of virus were available in viremic, susceptible monkeys to evoke primary antibody responses is compatible with the increased sensitivity of hosts to small “booster” injections of antigens; it does not necessarily infer that anamnestic antibody responses occur as a result of virus multiplication in previously infected hosts. Upon extrapolation to humans these findings suggest that a single endemic arthropod-borne virus can, upon transmission by vector mosquitoes, repeatedly stimulate anamnestic antibody responses in man and thus maintain detectable antibody levels and immunity throughout life. Moreover, in areas such as the Kanto Plain near Tokyo, Japan, where JE virus is the only known group B arthropod-borne virus, seasonal rises in HI and CF antibody titers to JE virus in persons with preseasonal homologous neutralizing (N) antibody need not imply that another group B virus exists in the same geographic region. HI, CF and N antibodies remained detectable in monkeys for at least 11 months after primary inapparent infection. HI and CF anamnestic antibody responses to large doses of JE virus were not significantly inhibited by high, preexisting HI, CF or N antibody levels in serum of hyperimmunized monkeys, but the effects of high antibody levels on anamnestic antibody responses to subsequent small virus doses were not conclusively ascertained.