Neutralization of Virus Infectivity by Antibodies: Old Problems in New Perspectives

Abstract

Neutralizing antibodies (NAbs) can be both sufficient and necessary for protection against viral infections, although they sometimes act in concert with cellular immunity. Successful vaccines against viruses induce NAbs but vaccine candidates against some major viral pathogens, including HIV-1, have failed to induce potent and effective such responses. Theories of how antibodies neutralize virus infectivity have been formulated and experimentally tested since the 1930s; and controversies about the mechanistic and quantitative bases for neutralization have continually arisen. Soluble versions of native oligomeric viral proteins that mimic the functional targets of neutralizing antibodies now allow the measurement of the relevant affinities of NAbs. Thereby the neutralizing occupancies on virions can be estimated and related to the potency of the NAbs. Furthermore, the kinetics and stoichiometry of NAb binding can be compared with neutralizing efficacy. Recently, the fundamental discovery that the intracellular factor TRIM21 determines the degree of neutralization of adenovirus has provided new mechanistic and quantitative insights. Since TRIM21 resides in the cytoplasm, it would not affect the neutralization of enveloped viruses, but its range of activity against naked viruses will be important to uncover. These developments bring together the old problems of virus neutralization—mechanism, stoichiometry, kinetics, and efficacy—from surprising new angles.

Antibody Responses to Zika Virus Infections in Environments of Flavivirus Endemicity

“…While virus neutralization assays measure a functional subset of antibodies and provide an important indicator of antiviral immunity, the best correlate of protection against viremia in DENV infection may be total polyclonal antibody titers, rather than neutralizing antibody titers (43). Antibodies that are weakly neutralizing in cell culture assays can contribute to physiologically important non-ADE mechanisms of virus clearance that are facilitated by receptor-mediated uptake and effector cells (48).…”

Supercritical Carbon Dioxide Extract of Seabuckthorn Leaves Enhances Rabies Virus Neutralizing Antibody Titers and CTL Response in Swiss Albino Mice

“…Vaccination against viral infections confers protection by generating neutralizing antibodies [24]. Since antibody production is crucial for the prevention of viral infections, we have shown that SCE300ET when administered along with Rb antigen, significantly enhanced the RVNA titres and the antibody titers were found to be higher as compared to Algel and rabies antigen immunized mice.…”

Intracellular Antiviral Immunity

“…Klasse: "Neutralization [….] is defined as the reduction in viral infectivity by the binding of antibodies to the surface of viral particles (virions), thereby blocking a step in the viral replication cycle that precedes virally encoded transcription or synthesis" (Klasse, 2014).…”