Analysis of the relationship between immunogenicity and immunity for viral subunit vaccines

Abstract

The prevention of viral infection by vaccination relies on stimulating an appropriate immune response in order to reduce the probability with which a virus can establish an infection. Post-vaccination antibody responses have therefore been associated with reducing the probability with which an individual can be infected (i.e., the vaccine's "impact"). Quantifying this relationship is essential in evaluating new vaccines, especially since comparisons between vaccines, and vaccine licensure, may be dependent on antibody responses alone. In this paper two principal questions are identified which need to be addressed in the evaluation of subunit vaccines: i) how do specific antibody levels relate to complete protection from infection or disease and ii) how do antigenic subunits interact in developing protection when combined together in a single vaccine. The aim is to identify explicitly certain assumptions that are frequently made implicitly in the discussion of vaccine action. First, antibody levels are related to levels of protection through a novel statistical analysis of incidence data from a published hepatitis B vaccine trial. The antibody response observed after influenza A virus infection is discussed in relation to the selection of neutralisation escape variants. Finally, by way of example, a theoretical situation is examined and three simple models of subunit vaccine action are constructed in order to describe how antibody levels may be related to population level phenomena such as the elimination of an infection by mass vaccination.

Cross‐neutralisation of antibodies elicited by an inactivated split‐virion influenza A/Vietnam/1194/2004 (H5N1) vaccine in healthy adults against H5N1 clade 2 strains

“…Protection from seasonal circulating human influenza A (H1N1 and H3N2) correlates with the detection of neutralising antibodies to the circulating strain 16 . This is usually measured using haemagglutination inhibition (HI) antibody titres with an antibody titre of 40 considered to provide a serological correlate of protection from infection 17 .…”

“…The protective effect of inactivated influenza vaccines is thought to be based on the induction of neutralising antibodies mainly to the viral HA. The measurement of neutralising antibodies therefore represents a valuable tool in predicting the actual protection of the vaccinated subject 16 . However, little is known about the correlation of neutralisation and HI titres and their respective correlation with immune protection against highly virulent wild‐type influenza strains.…”

“…Protection from seasonal circulating human influenza A (H1N1 and H3N2) correlates with the detection of neutralising antibodies to the circulating strain. 16 This is usually measured using haemagglutination inhibition (HI) antibody titres with an antibody titre of 40 considered to provide a serological correlate of protection from infection. 17 In the case of H5 influenza, serological correlates of protection have not been determined, but the use of neutralising antibody is considered an important approach to determine the presence of protective immunity.…”

Benchmarking B-Cell Epitope Prediction for the Design of Peptide-Based Vaccines: Problems and Prospects

“…B-cell epitope prediction is far more complicated for the neutralization of viruses and other infectious agents, in which case functionally relevant cross-reactivity may reflect emergent properties of the host-pathogen system that are left unaccounted for by analyses of the isolated pathogen or structural components thereof [79]. Synergy among pathogen virulence factors suggests the potential benefit of including more than one antigen in a vaccine; but it is difficult to predict which antigen combinations might afford protection against disease, as the interactions between immune responses to different antigens range from synergistic to antagonistic [80]. Much of this problem is due to uncertainty regarding the biological consequences of antibody-antigen binding, which tend to be highly context-dependent in ways that defy the intuitive notion of neutralization capacity as a monotonically increasing function of both antibody concentration and affinity for antigen [81].…”

Use of statistical models for evaluating antibody response as a correlate of protection against varicella

“…Furthermore, the antibody titre can often be shown to correlate with a vaccine's protective e cacy against the target disease [1][2][3]. The relationship between antibody titre and protective e cacy has led to the concept of a correlate of protection, which is often described as a protective level of antibody titre that can be used to determine whether a person is not protected and still susceptible to the disease or completely protected [3,4]. Although establishing a protective antibody level is desirable, identifying a clear-cut value is often impossible.…”