Absence of an All‐or‐None Type of Complement Requirement in Early Neutralizing Antibody against Western Equine Encephalitis Virus

Abstract

It has been established that rabbits and guinea pigs immunized or infected with herpes simplex virus develop early neutralizing antibody which functions only in the presence of complement (C') [9,[40][41][42]. This antibody was named C'-requiring neutralizing (CRN) antibody [40]. Herpetic infections of man also stimulate the development of CRN antibody in advance of ordinary neutralizing (N) antibody, so that the detection of CRN antibody in an early serum sample can give a positive diagnosis [42], although this means of early diagnosis decreases in practicability in the case of repeated infections among adults [12,20] [36,37] and simian herpes SA 8 viruses [29] have revealed occurrence of similar phenomena. However, the data presented have not necessarily coincided as to the extent to which the neutralizing activity of early serum is enhanced by C' as compared with that of late serum. In the case of herpes virus, early CRN antibody frequently far exceeds N antibody in level and, as a consequence, enhancement by C' of the neutralizing activity of such a serum is almost of the all-or-none type. A similar fact has been noted with vaccinia [23], bovine parainfluenza [17] and simian her-

Studies on the Neutralization of Herpes Simplex Virus

“…We suppose that such an effect of antibody may be influenced by the firmness of attachment as well as by the balance of molecular weights between virus and antibody. This supposition may be supported by two facts; firstly, affinity and valence play important roles in viral neutralization [5], whereas monovalent fragments of late IgG having a high affinity can neutralize bacteriophage as efficiently as bivalent IgG [20], and secondly reports previously reviewed [30] show a trend that antibody fragments neutralize smaller viruses more efficiently than larger viruses.…”

“…In line with this interpretation, Miyamoto et al [16] found that herpes virus antigens specific for CRN antibodies were located on the inner structures of the virion. Also such a CRN antibody as encountered in herpes virus infections, which markedly increases the endpoint in the presence of C', was not found in the case of small viruses such as WEE [30] ; this fact may be interpreted as indicating the ability of a lowaffinity antibody to neutralize small viruses. Further investigations will substantiate this theory.…”

“…In the case of cytomegalovirus, early and late IgG were equally enhanced by C' [8]. On the other hand, antibodies to smaller viruses such as WEE were not enhanced by C' so markedly even in the case of early serum [30].…”

Studies on the Neutralization of Herpes Simplex Virus

“…This was not the case, however, with poliovirus (14). Also, the CRN antibody response of some togaviruses was not so marked as in the case of HSV (34). Whether or not s-CRN antibody to these viruses exists will be a target for future studies.…”

Encephalitic Development in Alphaviral Infection

“…Early studies focused on antibody and complement. Yoshino, et al showed both early and late forming antibodies demonstrated enhanced virus neutralizing activity when in the presence of complement (Yoshino, et al, 1971). Jahrling et al demonstrated that immune elimination from immunized hamsters involved formation of virus/antibody aggregates cleared by the reticuloendothelial system.…”