Single-dose HPV vaccine immunity: is there a role for non-neutralizing antibodies?

Quang, Chau; Chung, Amy W.; Frazer, Ian H.; Toh, Zheng Quan; Licciardi, Paul V.

doi:10.1016/j.it.2022.07.011

Cited by 15 publications

(12 citation statements)

References 87 publications

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“…Antibody titres alone were not associated with protection, however, protection following parasite challenge was predicted by capacity for antibody-dependent cellular phagocytosis (ADCP) and FcγRIIIa engagement ( 69 , 71 ) as well as an immunoglobulin G (IgG) subclass distribution skewed towards IgG3 and away from IgG2 which would favour enhanced FcR engagement and effector functions ( 70 , 72 ). Furthermore, in the case of HIV-1 ( 73 ), human papillomavirus (HPV) ( 74 , 75 ), influenza ( 76 , 77 ), and SARS-CoV-2 ( 78 ), neutralising antibodies do not fully explain vaccination-induced humoral protection, suggesting a pertinent role for Fc effector functions in antibody-mediated immunity ( 51 , 79 , 80 ). This phenomenon has been well-described for the only moderately protective HIV-1 vaccine trial, RV144, which demonstrated partial efficacy in the absence of bnAbs ( 73 , 81 ); further antibody profiling indicated this phenomenon to be a consequence of robust Fc effector functions ( 73 , 82 , 83 ).…”

Section: Fc Effector Functions Enhance Antibody-mediated Protectionmentioning

confidence: 99%

Polyfunctional antibodies: a path towards precision vaccines for vulnerable populations

et al. 2023

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Vaccine efficacy determined within the controlled environment of a clinical trial is usually substantially greater than real-world vaccine effectiveness. Typically, this results from reduced protection of immunologically vulnerable populations, such as children, elderly individuals and people with chronic comorbidities. Consequently, these high-risk groups are frequently recommended tailored immunisation schedules to boost responses. In addition, diverse groups of healthy adults may also be variably protected by the same vaccine regimen. Current population-based vaccination strategies that consider basic clinical parameters offer a glimpse into what may be achievable if more nuanced aspects of the immune response are considered in vaccine design. To date, vaccine development has been largely empirical. However, next-generation approaches require more rational strategies. We foresee a generation of precision vaccines that consider the mechanistic basis of vaccine response variations associated with both immunogenetic and baseline health differences. Recent efforts have highlighted the importance of balanced and diverse extra-neutralising antibody functions for vaccine-induced protection. However, in immunologically vulnerable populations, significant modulation of polyfunctional antibody responses that mediate both neutralisation and effector functions has been observed. Here, we review the current understanding of key genetic and inflammatory modulators of antibody polyfunctionality that affect vaccination outcomes and consider how this knowledge may be harnessed to tailor vaccine design for improved public health.

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Section: Fc Effector Functions Enhance Antibody-mediated Protectionmentioning

confidence: 99%

Polyfunctional antibodies: a path towards precision vaccines for vulnerable populations

et al. 2023

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“…Human papillomavirus (HPV) vaccines have been highly efficacious in decreasing the incidence of HPV infection and cervical cancer worldwide [ 56 , 57 ]. These are typically administered as 2- or 3-dose regimes, yet recent observational studies suggest single-dose regimes to be as protective despite inducing significantly lower NAb titres (reviewed by Quang et al) [ 58 ]. The authors believe this protection may result from the activity of nNAb effector functions such as ADCP [ 58 ].…”

Section: Protective Functions Of Nnabsmentioning

confidence: 99%

“…These are typically administered as 2- or 3-dose regimes, yet recent observational studies suggest single-dose regimes to be as protective despite inducing significantly lower NAb titres (reviewed by Quang et al) [ 58 ]. The authors believe this protection may result from the activity of nNAb effector functions such as ADCP [ 58 ]. This merits further investigation as, if the immunological basis for these observations can be identified, this could strengthen arguments for the implementation of single-dose regimes vital for low-resource areas.…”

Section: Protective Functions Of Nnabsmentioning

confidence: 99%

Beyond bNAbs: Uses, Risks, and Opportunities for Therapeutic Application of Non-Neutralising Antibodies in Viral Infection

Mader,

Dustin

2024

Antibodies

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The vast majority of antibodies generated against a virus will be non-neutralising. However, this does not denote an absence of protective capacity. Yet, within the field, there is typically a large focus on antibodies capable of directly blocking infection (neutralising antibodies, NAbs) of either specific viral strains or multiple viral strains (broadly-neutralising antibodies, bNAbs). More recently, a focus on non-neutralising antibodies (nNAbs), or neutralisation-independent effects of NAbs, has emerged. These can have additive effects on protection or, in some cases, be a major correlate of protection. As their name suggests, nNAbs do not directly neutralise infection but instead, through their Fc domains, may mediate interaction with other immune effectors to induce clearance of viral particles or virally infected cells. nNAbs may also interrupt viral replication within infected cells. Developing technologies of antibody modification and functionalisation may lead to innovative biologics that harness the activities of nNAbs for antiviral prophylaxis and therapeutics. In this review, we discuss specific examples of nNAb actions in viral infections where they have known importance. We also discuss the potential detrimental effects of such responses. Finally, we explore new technologies for nNAb functionalisation to increase efficacy or introduce favourable characteristics for their therapeutic applications.

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“…In fact, several studies have shown how the administration of a single dose of an HPV vaccine results in the appearance of neutralizing antibodies which, although present at a lower titer when compared to those that appear following two or three dose schedules, are able to prevent infection with the virus and prevent the appearance of precancerous lesions at the level of the cervix. Moreover, immunity also appears to be mediated by non-neutralizing antibodies and neutrophil degranulation, and the avidity indexes of antibodies directed toward the L1 protein are very similar to those of individuals receiving three doses [ 74 , 75 ]. Both the Gardasil and Cervarix vaccines induce cross-protection against nonvaccine types such as HPV 31 and HPV 45 but with lower antibody titers than the epitopes included in the vaccines [ 76 , 77 ].…”

Section: Preventionmentioning

confidence: 99%

Human Papillomavirus Epidemiology and Prevention: Is There Still a Gender Gap?

et al. 2023

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Background and aim: Human papillomavirus (HPV) is sexually transmitted, one of the three most common sexually transmitted infections (STIs) in both males and females, and the most common viral STI. A crucial public health strategy to protect people against HPV is vaccination, which has shown its effectiveness in preventing HPV-related diseases. Presently, three types of vaccines are available (bivalent, quadrivalent, and nonvalent), and they all target the two most oncogenic virus genotypes (HPV 16 and 18). In recent years, the need to implement vaccination programmes that include all genders has been discussed in order to achieve herd immunity against HPV. To date, only a few countries have included young males in their vaccination programmes. Thus, our objective with this review is to provide an overview of the epidemiology of HPV and HPV prevention strategies and report the latest findings from the scientific literature.

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Single-dose HPV vaccine immunity: is there a role for non-neutralizing antibodies?

Cited by 15 publications

References 87 publications

Polyfunctional antibodies: a path towards precision vaccines for vulnerable populations

Polyfunctional antibodies: a path towards precision vaccines for vulnerable populations

Beyond bNAbs: Uses, Risks, and Opportunities for Therapeutic Application of Non-Neutralising Antibodies in Viral Infection

Human Papillomavirus Epidemiology and Prevention: Is There Still a Gender Gap?

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