New developments in an old strategy: heterologous vector primes and envelope protein boosts in HIV vaccine design

Musich, Thomas; Robert-Guroff, Marjorie

doi:10.1586/14760584.2016.1158108

Cited by 11 publications

(9 citation statements)

References 166 publications

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“…For instance, scarification has traditionally been used to percutaneously deliver attenuated poxviruses as a highly effective smallpox vaccine (25). Moreover, combining different vector systems in heterologous prime-boost regimens often results in more potent immune responses (26). This often includes the use of DNA plasmids as the priming agent because it has been shown that DNA vaccines are safe and induce potent CTL responses, whereas there is no vector immunity (27).…”

Section: Importancementioning

confidence: 99%

Priming with a Potent HIV-1 DNA Vaccine Frames the Quality of Immune Responses prior to a Poxvirus and Protein Boost

Asbach

Kibler

Köstler

et al. 2019

J Virol

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The use of heterologous immunization regimens and improved vector systems has led to increases in immunogenicity of HIV-1 vaccine candidates in nonhuman primates. In order to resolve interrelations between different delivery modalities, three different poxvirus boost regimens were compared. Three groups of rhesus macaques were each primed with the same DNA vaccine encoding Gag, Pol, Nef, and gp140. The groups were then boosted with either the vaccinia virus strain NYVAC or a variant with improved replication competence in human cells, termed NYVAC-KC. The latter was administered either by scarification or intramuscularly. Finally, macaques were boosted with adjuvanted gp120 protein to enhance humoral responses. The regimen elicited very potent CD4+ and CD8+ T cell responses in a well-balanced manner, peaking 2 weeks after the boost. T cells were broadly reactive and polyfunctional. All animals exhibited antigen-specific humoral responses already after the poxvirus boost, which further increased following protein administration. Polyclonal reactivity of IgG antibodies was highest against HIV-1 clade C Env proteins, with considerable cross-reactivity to other clades. Substantial effector functional activities (antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated virus inhibition) were observed in serum obtained after the last protein boost. Notably, major differences between the groups were absent, indicating that the potent priming induced by the DNA vaccine initially framed the immune responses in such a way that the subsequent boosts with NYVAC and protein led only to an increase in the response magnitudes without skewing the quality. This study highlights the importance of selecting the best combination of vector systems in heterologous prime-boost vaccination regimens. IMPORTANCE The evaluation of HIV vaccine efficacy trials indicates that protection would most likely correlate with a polyfunctional immune response involving several effector functions from all arms of the immune system. Heterologous prime-boost regimens have been shown to elicit vigorous T cell and antibody responses in nonhuman primates that, however, qualitatively and quantitatively differ depending on the respective vector systems used. The present study evaluated a DNA prime and poxvirus and protein boost regimen and compared how two poxvirus vectors with various degrees of replication capacity and two different delivery modalities—conventional intramuscular delivery and percutaneous delivery by scarification—impact several immune effectors. It was found that despite the different poxvirus boosts, the overall immune responses in the three groups were similar, suggesting the potent DNA priming as the major determining factor of immune responses. These findings emphasize the importance of selecting optimal priming agents in heterologous prime-boost vaccination settings.

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Section: Importancementioning

confidence: 99%

Priming with a Potent HIV-1 DNA Vaccine Frames the Quality of Immune Responses prior to a Poxvirus and Protein Boost

Asbach

Kibler

Köstler

et al. 2019

J Virol

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“…However, the prime-boost immunization strategy is still an alternative approach for finding a cure against this important pathogen. For many years, research was focused on the induction of humoral immunity as the main arm of the adaptive immune response for a successful vaccine, but cellular immune responses have emerged as a key arm against the infected cells and viral reservoirs (43).…”

Section: Some Lessons Learned From Complementary Prime-boost Immunizamentioning

confidence: 99%

Can Complementary Prime-Boost Immunization Strategies Be an Alternative and Promising Vaccine Approach Against Dengue Virus?

et al. 2019

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Dengue is one of the most important diseases transmitted by mosquitoes. Dengvaxia®, a vaccine registered in several countries, cannot be administered to non-immune individuals and children younger than 9 years old, due to safety reasons. There are two vaccine candidates in phase 3 efficacy trials, but their registration date is completely unknown at this moment. So, the development of new vaccines or vaccine strategies continues to be a priority for the WHO. This work reviews some complementary prime-boost immunization studies against important human pathogens. Additionally, it reviews the results obtained using this regimen of immunization against dengue virus as a potential alternative approach for finding a safe and efficient vaccine. Finally, the main elements associated with this strategy are also discussed. The generation of new strategies of vaccination against dengue virus, must be directed to reduce the risk of increasing viral load through sub-neutralizing antibodies and it must be also directed to induce a polyfunctional T cell response. Complementary prime-boost immunization strategies could emerge as an interesting approach to induce solid immunity or at least to reduce viral load after natural infection, avoiding severe dengue. Subunit vaccine could be safe and attractive antigens for this strategy, especially proteins including B, and T-cells epitopes for inducing humoral and cellular immune responses, which can play an important role controlling the disease.

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“…The prime-boost strategy has recently gained popularity and is a commonly used approach. In this setting, the immune system is primed by one vaccine candidate and boosted with either the same (homologous) or a different (heterologous) vaccine candidate (23). To understand the impacts of different boosts on the same prime, we made use of the RV132 and RV135 vaccine trials (the latter was a precursor study to the RV144 trial), in which the same prime, ALVAC, was boosted with either bivalent gp120 (bi-gp120), oligomeric gp160 (o-gp160), or AIDSVAX (A244) (24,25).…”

Section: Resultsmentioning

confidence: 99%

Modulation of Vaccine-Induced CD4 T Cell Functional Profiles by Changes in Components of HIV Vaccine Regimens in Humans

Pissani

Schulte

Eller

et al. 2018

J Virol

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To date, six vaccine strategies have been evaluated in clinical trials for their efficacy at inducing protective immune responses against HIV infection. However, only the ALVAC-HIV/AIDSVAX B/E vaccine (RV144 trial) has demonstrated protection, albeit modestly (31%; = 0.03). One potential correlate of protection was a low-frequency HIV-specific CD4 T cell population with diverse functionality. Although CD4 T cells, particularly T follicular helper (Tfh) cells, are critical for effective antibody responses, most studies involving HIV vaccines have focused on humoral immunity or CD8 T cell effector responses, and little is known about the functionality and frequency of vaccine-induced CD4 T cells. We therefore assessed responses from several phase I/II clinical trials and compared them to responses to natural HIV-1 infection. We found that all vaccines induced a lower magnitude of HIV-specific CD4 T cell responses than that observed for chronic infection. Responses differed in functionality, with a CD40 ligand (CD40L)-dominated response and more Tfh cells after vaccination, whereas chronic HIV infection provoked tumor necrosis factor alpha (TNF-α)-dominated responses. The vaccine delivery route further impacted CD4 T cells, showing a stronger Th1 polarization after dendritic cell delivery than after intramuscular vaccination. In prime/boost regimens, the choice of prime and boost influenced the functional profile of CD4 T cells to induce more or less polyfunctionality. In summary, vaccine-induced CD4 T cell responses differ remarkably between vaccination strategies, modes of delivery, and boosts and do not resemble those induced by chronic HIV infection. Understanding the functional profiles of CD4 T cells that best facilitate protective antibody responses will be critical if CD4 T cell responses are to be considered a clinical trial go/no-go criterion. Only one HIV-1 candidate vaccine strategy has shown protection, albeit marginally (31%), against HIV-1 acquisition, and correlates of protection suggested that a multifunctional CD4 T cell immune response may be important for this protective effect. Therefore, the functional phenotypes of HIV-specific CD4 T cell responses induced by different phase I and phase II clinical trials were assessed to better show how different vaccine strategies influence the phenotype and function of HIV-specific CD4 T cell immune responses. The significance of this research lies in our comprehensive comparison of the compositions of the T cell immune responses to different HIV vaccine modalities. Specifically, our work allows for the evaluation of vaccination strategies in terms of their success at inducing Tfh cell populations.

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New developments in an old strategy: heterologous vector primes and envelope protein boosts in HIV vaccine design

Cited by 11 publications

References 166 publications

Priming with a Potent HIV-1 DNA Vaccine Frames the Quality of Immune Responses prior to a Poxvirus and Protein Boost

Priming with a Potent HIV-1 DNA Vaccine Frames the Quality of Immune Responses prior to a Poxvirus and Protein Boost

Can Complementary Prime-Boost Immunization Strategies Be an Alternative and Promising Vaccine Approach Against Dengue Virus?

Modulation of Vaccine-Induced CD4 T Cell Functional Profiles by Changes in Components of HIV Vaccine Regimens in Humans

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