IgG Subtype Is Correlated with Efficiency of Passive Protection and Effector Function of Anti-Herpes Simplex Virus Glycoprotein D Monoclonal Antibodies

Ishizaka, Sally T.; Piacente, Priscilla; Silva, Jillian; Mishkin, Eric M.

doi:10.1093/infdis/172.4.1108

Cited by 50 publications

(32 citation statements)

References 12 publications

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“…Induction of IgG2a with enhanced complement-fixing capability is one of the hallmarks of a Th1 response profile in mice and provided superior protection against HSV challenge (62,63). We also observed the induction of strong HSV-2 neutralizing antibody titers in GEN-003/MM-2-immunized mice, which was induced by the gD2 antigen (data not shown).…”

Section: Discussionmentioning

confidence: 64%

An Adjuvanted Herpes Simplex Virus 2 Subunit Vaccine Elicits a T Cell Response in Mice and Is an Effective Therapeutic Vaccine in Guinea Pigs

Škoberne

Cardin

Lee

et al. 2013

J Virol

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bImmunotherapeutic herpes simplex virus 2 (HSV-2) vaccine efficacy depends upon the promotion of antigen-specific immune responses that inhibit reactivation or reactivated virus, thus controlling both recurrent lesions and viral shedding. In the present study, a candidate subunit vaccine, GEN-003/MM-2, was evaluated for its ability to induce a broad-spectrum immune response in mice and therapeutic efficacy in HSV-2-infected guinea pigs. GEN-003 is comprised of HSV-2 glycoprotein D2 (gD2⌬TMR 340-363 ) and a truncated form of infected cell polypeptide 4 (ICP4 383-766 ), formulated with Matrix M-2 (MM-2) adjuvant (GEN-003/MM-2). In addition to eliciting humoral immune responses, CD4؉ and CD8 ؉ T cells characterized by the secretion of multiple cytokines and cytolytic antigen-specific T cell responses that were able to be recalled at least 44 days after the last immunization were induced in immunized mice. Furthermore, vaccination with either GEN-003 or GEN-003/MM-2 led to significant reductions in both the prevalence and severity of lesions in HSV-2-infected guinea pigs compared to those of phosphate-buffered saline (PBS) control-vaccinated animals. While vaccination with MM-2 adjuvant alone decreased recurrent disease symptoms compared to the PBS control group, the difference was not statistically significant. Importantly, the frequency of recurrent viral shedding was considerably reduced in GEN-003/MM-2-vaccinated animals but not in GEN-003-or MM-2-vaccinated animals. These findings suggest a possible role for immunotherapeutic GEN-003/MM-2 vaccination as a viable alternative to chronic antiviral drugs in the treatment and control of genital herpes disease. H erpes simplex virus 2 (HSV-2) is one of the most prevalent sexually transmitted diseases, having infected more than 500 million people worldwide, with an estimated 23 million new infections occurring annually (1). HSV-2 infects epithelial cells of the genital mucosa during primary infection, followed by the establishment of latency in neuronal dorsal root ganglia via retrograde transport along nerve axons. Throughout latency, virus can reactivate, causing genital lesions and/or asymptomatic shedding of virus. Although suppressive antiviral therapy has shown promise in reducing both symptomatic recurrent lesions and overall viral shedding, subclinical HSV reactivation persists, likely contributing significantly to the observed continued transmission (2). The development of an efficacious immunotherapeutic vaccine targeting HSV-2 likely represents the best strategy for preventing both lesion outbreaks and the continued spread of virus.Despite considerable effort, all vaccine candidates to date have failed to meet their defined endpoints in clinical trials. The majority of clinical trials to date have focused on prophylactic subunit vaccines, largely using the HSV-2 surface glycoproteins as immunogens. The viral envelope glycoproteins gD and gB are the dominant targets for neutralizing antibody production (3, 4), making them logical candidates for vaccine devel...

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Section: Discussionmentioning

confidence: 64%

An Adjuvanted Herpes Simplex Virus 2 Subunit Vaccine Elicits a T Cell Response in Mice and Is an Effective Therapeutic Vaccine in Guinea Pigs

Škoberne

Cardin

Lee

et al. 2013

J Virol

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“…Accordingly, we previously observed IgG2a-dominated humoral immune responses after a similar immunization against the likewise glycosylated viral surface proteins hemagglutinin of influenza A or F of the respiratory syncytial virus (43). Intriguingly, IgG1 has been shown to be inferior to IgG2a with regard to protection from viral infections (44)(45)(46). Furthermore, even neutralizing Abs against influenza virus and HIV-1 demonstrate enhanced protection if expressed with an IgG2a Fc domain (8,47).…”

Section: Discussionmentioning

confidence: 97%

Enhancing the Quality of Antibodies to HIV-1 Envelope by GagPol-Specific Th Cells

Bonsmann

Niezold

Temchura

et al. 2015

The Journal of Immunology

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The importance of Fc-dependent effector functions of Abs induced by vaccination is increasingly recognized. However, vaccination of mice against HIV envelope (Env) induced a skewed Th cell response leading to Env-specific Abs with reduced effector function. To overcome this bias, GagPol-specific Th cells were harnessed to provide intrastructural help for Env-specific B cells after immunization with virus-like particles containing GagPol and Env. This led to a balanced Env-specific humoral immune response with a more inflammatory Fc glycan profile. The increased quality in the Ab response against Env was confirmed by FcγR activation assays. Because the Env-specific Th cell response was also biased in human vaccinees, intrastructural help is an attractive novel approach to increase the efficacy of prophylactic HIV Env-based vaccines and may also be applicable to other particulate vaccines.

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“…To avoid this pitfall, switch mutants can be derived from a given monoclonal antibody. This approach has shown that IgG2a antibodies directed against herpes simplex virus (14) and yellow fever virus (27) were the most protective in vivo. However, with anti-Sindbis virus antibodies, no evidence that the IgG subclass is important for in vitro clearance of the virus was found but the IgG2a isotype was not included in the study (30).…”

mentioning

confidence: 99%

Increased Efficacy of the Immunoglobulin G2a Subclass in Antibody-Mediated Protection against Lactate Dehydrogenase-Elevating Virus-Induced Polioencephalomyelitis Revealed with Switch Mutants

Markine-Goriaynoff

Coutelier

2002

J Virol

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Immunoglobulin G1 (IgG1), IgG2a, and IgG2b switch variants were derived from an IgG3 monoclonal antibody directed against the VP3 envelope glycoprotein of lactate dehydrogenase-elevating virus (LDV). Among the four antibodies, IgG2a delayed the onset and progression of LDV-induced polioencephalomyelitis more than did the other subclasses. This suggests that the IgG2a predominance observed in many IgG antibody responses elicited by live viruses could, at least under some circumstances, correspond to the selection of the best protection for the infected host.

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IgG Subtype Is Correlated with Efficiency of Passive Protection and Effector Function of Anti-Herpes Simplex Virus Glycoprotein D Monoclonal Antibodies

Cited by 50 publications

References 12 publications

An Adjuvanted Herpes Simplex Virus 2 Subunit Vaccine Elicits a T Cell Response in Mice and Is an Effective Therapeutic Vaccine in Guinea Pigs

An Adjuvanted Herpes Simplex Virus 2 Subunit Vaccine Elicits a T Cell Response in Mice and Is an Effective Therapeutic Vaccine in Guinea Pigs

Enhancing the Quality of Antibodies to HIV-1 Envelope by GagPol-Specific Th Cells

Increased Efficacy of the Immunoglobulin G2a Subclass in Antibody-Mediated Protection against Lactate Dehydrogenase-Elevating Virus-Induced Polioencephalomyelitis Revealed with Switch Mutants

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