UV-inactivated vaccinia virus (VV) in a multi-envelope DNA-VV-protein (DVP) HIV-1 vaccine protects macaques from lethal challenge with heterologous SHIV

Jones, Bart G.; Sealy, Robert E.; Zhan, Xiaoyan; Freiden, Pamela; Surman, Sherri L.; Blanchard, James; Hurwitz, Julia L.

doi:10.1016/j.vaccine.2012.03.001

Cited by 12 publications

(11 citation statements)

References 34 publications

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“…UV has also been used to inactivate viruses in the past and such UV-inactivated viruses are able to induce protective humoral immunity [61,62]. Surprisingly, UV-inactivated Nakayama virus only weakly bound anti-JEV MHIAF and T16 MAb when assessed by Western blot analysis, which indicates that the antigenic structure of Nakayama virus might be severely altered by UV irradiation (Fig 8B).…”

Section: Neutralizing Activity Of the Ediii 329/331/389-specific Antimentioning

confidence: 98%

Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III

et al. 2015

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Formalin-inactivated Japanese encephalitis virus (JEV) vaccines are widely available, but the effects of formalin inactivation on the antigenic structure of JEV and the profile of antibodies elicited after vaccination are not well understood. We used a panel of monoclonal antibodies (MAbs) to map the antigenic structure of live JEV virus, untreated control virus (UCV), formalin-inactivated commercial vaccine (FICV), and formalin-inactivated virus (FIV). The binding activity of T16 MAb against Nakayama-derived FICV and several strains of FIV was significantly lower compared to live virus and UCV. T16 MAb, a weakly neutralizing JEV serocomplex antibody, was found to inhibit JEV infection at the post-attachment step. The T16 epitope was mapped to amino acids 329, 331, and 389 within domain III (EDIII) of the envelope (E) glycoprotein. When we explored the effect of formalin inactivation on the immunogenicity of JEV, we found that Nakayama-derived FICV, FIV, and UCV all exhibited similar immunogenicity in a mouse model, inducing anti-JEV and anti-EDII 101/106/107 epitope-specific antibodies. However, the EDIII 329/331/389 epitope-specific IgG antibody and neutralizing antibody titers were significantly lower for FICV-immunized and FIV-immunized mouse serum than for UCV-immunized. Formalin inactivation seems to alter the antigenic structure of the E protein, which may reduce the potency of commercially available JEV vaccines. Virus inactivation by H2O2, but not by UV or by short-duration and higher temperature formalin treatment, is able to maintain the antigenic structure of the JEV E protein. Thus, an alternative inactivation method, such as H2O2, which is able to maintain the integrity of the E protein may be essential to improving the potency of inactivated JEV vaccines.

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Section: Neutralizing Activity Of the Ediii 329/331/389-specific Antimentioning

confidence: 98%

Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III

et al. 2015

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“…Despite the eradication of smallpox by widespread vaccination with vaccinia virus, the potential use of smallpox as a bioweapon (72) and the importance of using vaccinia virus as an expression vector for immunization against other infectious diseases (73–75) and cancer (76–77), make the understanding of immune responses to vaccinia virus extremely important. In this study, we have evaluated IFNγ-CD4+ T cell responses and antibody responses against the vaccinia proteins A27L, A33R, B5R and L1R in a large set of vaccinia virus-vaccinated donors.…”

Section: Discussionmentioning

confidence: 99%

CD4+ T Cells Provide Intermolecular Help To Generate Robust Antibody Responses in Vaccinia Virus–Vaccinated Humans

Yin

Calvo‐Calle

Cruz

et al. 2013

The Journal of Immunology

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Immunization with vaccinia virus elicits a protective antibody response that is almost completely CD4+ T cell dependent. A recent study in a rodent model observed a deterministic linkage between antibody and CD4+ T cell responses to particular vaccinia virus proteins suggesting that CD4+ T cell help is preferentially provided to B cells with the same protein specificity (Sette A et al., Immunity 2008, 847–858). However, a causal linkage between antibody and CD4+ T cell responses to vaccinia or any other large pathogen in humans has yet to be done. In this study, we measured the antibody and CD4+ T cell responses against four vaccinia viral proteins (A27L, A33R, B5R, and L1R) known to be strongly targeted by humoral and cellular responses induced by vaccinia virus-vaccination in 90 recently vaccinated and 7 long-term vaccinia-immunized human donors. Our data indicate that there is no direct linkage between antibody and CD4+ T cell responses against each individual protein in both short-term and long-term immunized donors. Together with the observation that the presence of immune responses to these four proteins is linked together within donors, our data suggest that in vaccinia-immunized humans, individual viral proteins are not the primary recognition unit of CD4+ T cell help for B cells. Therefore, we have for the first time showed evidence that CD4+ T cells provide intermolecular (also known as non-cognate or heterotypic) help to generate robust antibody responses against four vaccinia viral proteins in humans.

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“…As with other chronic infections (e.g., varicella zoster virus), a protective immune response may prevent exogenous virus infection, but may fail to clear endogenous virus, highlighting the importance of vaccinating individuals before a pathogen exposure has occurred. A multienvelope HIV vaccine approach, using dozens of envelopes, has proven protective against disease caused by a heterologous SHIV challenge in macaques (26,58) and has proven safe and immunogenic in an abbreviated clinical trial (8,25,45). Taken together, these results encourage continued testing of the strategy and simplification of cocktails to support advanced clinical studies.…”

Section: Tackling Diverse Pathogens With Human Vaccinesmentioning

confidence: 91%

“…In this study, we describe mouse immunizations with either gp140 or gp120 envelope proteins, forms of envelope that have been associated with vaccine efficacy in previous nonhuman primate studies and in the partially successful RV144 study (26,41,58). Monoclonal antibodies produced from immunized mice were tested for binding to a small panel of envelope antigens.…”

mentioning

confidence: 99%

Murine Monoclonal Antibodies for Antigenic Discrimination of HIV-1 Envelope Proteins

et al. 2016

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UV-inactivated vaccinia virus (VV) in a multi-envelope DNA-VV-protein (DVP) HIV-1 vaccine protects macaques from lethal challenge with heterologous SHIV

Cited by 12 publications

References 34 publications

Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III

Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III

CD4+ T Cells Provide Intermolecular Help To Generate Robust Antibody Responses in Vaccinia Virus–Vaccinated Humans

Murine Monoclonal Antibodies for Antigenic Discrimination of HIV-1 Envelope Proteins

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