Abstract
Live-attenuated vaccines (LAVs) have achieved remarkable successes in controlling virus spread, as well as for other applications such as cancer immunotherapy. However, with rapid increases in international travel, globalization, geographic spread of viral vectors, and widespread use of vaccines, there is an increasing need to consider how pre-exposure to viruses which share similar antigenic regions can impact vaccine efficacy. Pre-existing antibodies, derived from either from maternal–fetal transmission, or by previous infection or vaccination, have been demonstrated to interfere with vaccine immunogenicity of measles, adenovirus, and influenza LAVs. Immune interference of LAVs can be caused by the formation of virus–antibody complexes that neutralize virus infection in antigen-presenting cells, or by the cross-linking of the B-cell receptor with the inhibitory receptor, FcγRIIB. On the other hand, pre-existing antibodies can augment flaviviral LAV efficacy such as that of dengue and yellow fever virus, especially when pre-existing antibodies are present at sub-neutralizing levels. The increased vaccine immunogenicity can be facilitated by antibody-dependent enhancement of virus infection, enhancing virus uptake in antigen-presenting cells, and robust induction of innate immune responses that promote vaccine immunogenicity. This review examines the literature on this topic and examines the circumstances where pre-existing antibodies can inhibit or enhance LAV efficacy. A better knowledge of the underlying mechanisms involved could allow us to better manage immunization in seropositive individuals and even identify possibilities that could allow us to exploit pre-existing antibodies to boost vaccine-induced responses for improved vaccine efficacy.
Highlights
Live-attenuated vaccines (LAVs) have achieved remarkable successes in controlling virus spread, as well as for other applications such as cancer immunotherapy
This review examines the literature on this topic and examines the circumstances where pre-existing antibodies can inhibit or enhance LAV efficacy
The clinical trial finding that subjects with a limited range of cross-reactive antibodies from a prior Japanese Encephalitis vaccine were able to enhance yellow fever vaccination, by prolonging vaccine viremia duration that leads to higher antibody titers, hints at the possibility that whether pre-existing antibodies inhibit or augment flavivirus infection will depend on both antibody titers and the type/specificity of antibodies produced [85]
Summary
“It’s time to close the book on infectious diseases, declare the war against pestilence won, and shift national resources to such chronic problems as cancer and heart disease” [1]. Comprised of living but attenuated microorganisms, this group, which includes replication-competent viral vectors, retains the capacity to replicate in vivo but does not cause disease in humans Due to their ability to mimic a natural infection and activate innate immune responses, LAVs are able to induce long-lasting, robust cellular and humoral immune responses without the need for adjuvants [13]. LAVs contain a repertoire of antigens similar to the wild-type organism, allowing them to present all epitopes in their native conformation to antigen-presenting cells [15] Given their potential in activating robust CD8+ and CD4+ responses, polio, recombinant vesicular stomatitis virus (VSV), recombinant adenovirus, and attenuated measles vaccines have been proposed as potential viral vectors for the delivery of tumor antigens [16,17]. A better understanding will allow us to tailor our vaccination schedules or vaccine doses, to ensure that LAV efficacy will not be compromised by the presence of pre-existing immunity
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