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Immunotherapy with an HIV-DNA Vaccine in Children and Adults.

Palma P, Gudmundsdotter L, Finocchi A, Eriksson LE, Mora N, Santilli V, Aquilani A, Manno EC, Zangari P, Romiti ML, Montesano C, Grifoni A, Brave A, Ljungberg K, Blomberg P, Bernardi S, Sandström E, Hejdeman B, Rossi P, Wahren B - Vaccines (Basel) (2014)

Bottom Line: The HIV-DNA vaccine was generally well tolerated, and no serious adverse events were registered in any group.In conclusion, the HIV-DNA vaccine can elicit new HIV-specific cellular immune responses, particularly to Gag antigens, in both HIV-infected children and adults.No severe adverse effects related to the vaccine were found in either cohort, and no virological failures or drug resistances were detected.

View Article: PubMed Central - PubMed

Affiliation: University Department of Pediatrics (DPUO), Unit of Immune and Infectious Diseases, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy. paolo.palma@opbg.net.

ABSTRACT
Therapeutic HIV immunization is intended to induce new HIV-specific cellular immune responses and to reduce viral load, possibly permitting extended periods without antiretroviral drugs. A multigene, multi-subtype A, B, C HIV-DNA vaccine (HIVIS) has been used in clinical trials in both children and adults with the aim of improving and broadening the infected individuals' immune responses. Despite the different country locations, different regimens and the necessary variations in assays performed, this is, to our knowledge, the first attempt to compare children's and adults' responses to a particular HIV vaccine. Ten vertically HIV-infected children aged 4-16 years were immunized during antiretroviral therapy (ART). Another ten children were blindly recruited as controls. Both groups continued their antiretroviral treatment during and after vaccinations. Twelve chronically HIV-infected adults were vaccinated, followed by repeated structured therapy interruptions (STI) of their antiretroviral treatment. The adult group included four controls, receiving placebo vaccinations. The HIV-DNA vaccine was generally well tolerated, and no serious adverse events were registered in any group. In the HIV-infected children, an increased specific immune response to Gag and RT proteins was detected by antigen-specific lymphoproliferation. Moreover, the frequency of HIV-specific CD8+ T-cell lymphocytes releasing perforin was significantly higher in the vaccinees than the controls. In the HIV-infected adults, increased CD8+ T-cell responses to Gag, RT and viral protease peptides were detected. No augmentation of HIV-specific lymphoproliferative responses were detected in adults after vaccination. In conclusion, the HIV-DNA vaccine can elicit new HIV-specific cellular immune responses, particularly to Gag antigens, in both HIV-infected children and adults. Vaccinated children mounted transient new HIV-specific immune responses, including both CD4+ T-cell lymphoproliferation and late CD8+ T-cell responses. In the adult cohort, primarily CD8+ T-cell responses related to MHC class I alleles were noted. However, no clinical benefits with respect to viral load reduction were ascribable to the vaccinations alone. No severe adverse effects related to the vaccine were found in either cohort, and no virological failures or drug resistances were detected.

No MeSH data available.


Increases of HIV-specific and recall-induced IFN-γ ELISpot responses in placebo and vaccine recipients in the adult cohort. Changes (Ch.) in HIV-specific IFN-γ (IFNg) responses to Gag, RT and protease peptides at visit 10 are shown. The baseline responses have been subtracted. The vaccine group had more prominent increases of HIV-specific IFN-γ responses of peptide reactivities than the placebo group (Mann–Whitney U test, p = 0.028).
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vaccines-02-00563-f003: Increases of HIV-specific and recall-induced IFN-γ ELISpot responses in placebo and vaccine recipients in the adult cohort. Changes (Ch.) in HIV-specific IFN-γ (IFNg) responses to Gag, RT and protease peptides at visit 10 are shown. The baseline responses have been subtracted. The vaccine group had more prominent increases of HIV-specific IFN-γ responses of peptide reactivities than the placebo group (Mann–Whitney U test, p = 0.028).

Mentions: The adult vaccine group had a higher net gain of HIV-specific IFN-γ responses from baseline to Week 10 compared to the placebo group (p = 0.028, Figure 3). The levels of perforin-secreting cells were high at baseline. There were distinct increases of peptide-specific responses as measured by ELISpot IFN-γ to peptides representing HIV-1 subtype B. Altogether, 28 responses occurred in the vaccinated cohort and 11 in the placebo group. They were tentatively allocated to alleles HLA (Human Leucocyte Antigen) A*0201, A*0301, B*35 and B*5701, among others, and occurred for several peptides summarized to represent Gag, RT and viral protease PR (Figure 3) [22]. We must therefore conclude that vaccination, together with STI, permitting viral stimulation, contributed to the detection of the novel HIV-specific CD8+ T-cell responses.


Immunotherapy with an HIV-DNA Vaccine in Children and Adults.

Palma P, Gudmundsdotter L, Finocchi A, Eriksson LE, Mora N, Santilli V, Aquilani A, Manno EC, Zangari P, Romiti ML, Montesano C, Grifoni A, Brave A, Ljungberg K, Blomberg P, Bernardi S, Sandström E, Hejdeman B, Rossi P, Wahren B - Vaccines (Basel) (2014)

Increases of HIV-specific and recall-induced IFN-γ ELISpot responses in placebo and vaccine recipients in the adult cohort. Changes (Ch.) in HIV-specific IFN-γ (IFNg) responses to Gag, RT and protease peptides at visit 10 are shown. The baseline responses have been subtracted. The vaccine group had more prominent increases of HIV-specific IFN-γ responses of peptide reactivities than the placebo group (Mann–Whitney U test, p = 0.028).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494215&req=5

vaccines-02-00563-f003: Increases of HIV-specific and recall-induced IFN-γ ELISpot responses in placebo and vaccine recipients in the adult cohort. Changes (Ch.) in HIV-specific IFN-γ (IFNg) responses to Gag, RT and protease peptides at visit 10 are shown. The baseline responses have been subtracted. The vaccine group had more prominent increases of HIV-specific IFN-γ responses of peptide reactivities than the placebo group (Mann–Whitney U test, p = 0.028).
Mentions: The adult vaccine group had a higher net gain of HIV-specific IFN-γ responses from baseline to Week 10 compared to the placebo group (p = 0.028, Figure 3). The levels of perforin-secreting cells were high at baseline. There were distinct increases of peptide-specific responses as measured by ELISpot IFN-γ to peptides representing HIV-1 subtype B. Altogether, 28 responses occurred in the vaccinated cohort and 11 in the placebo group. They were tentatively allocated to alleles HLA (Human Leucocyte Antigen) A*0201, A*0301, B*35 and B*5701, among others, and occurred for several peptides summarized to represent Gag, RT and viral protease PR (Figure 3) [22]. We must therefore conclude that vaccination, together with STI, permitting viral stimulation, contributed to the detection of the novel HIV-specific CD8+ T-cell responses.

Bottom Line: The HIV-DNA vaccine was generally well tolerated, and no serious adverse events were registered in any group.In conclusion, the HIV-DNA vaccine can elicit new HIV-specific cellular immune responses, particularly to Gag antigens, in both HIV-infected children and adults.No severe adverse effects related to the vaccine were found in either cohort, and no virological failures or drug resistances were detected.

View Article: PubMed Central - PubMed

Affiliation: University Department of Pediatrics (DPUO), Unit of Immune and Infectious Diseases, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy. paolo.palma@opbg.net.

ABSTRACT
Therapeutic HIV immunization is intended to induce new HIV-specific cellular immune responses and to reduce viral load, possibly permitting extended periods without antiretroviral drugs. A multigene, multi-subtype A, B, C HIV-DNA vaccine (HIVIS) has been used in clinical trials in both children and adults with the aim of improving and broadening the infected individuals' immune responses. Despite the different country locations, different regimens and the necessary variations in assays performed, this is, to our knowledge, the first attempt to compare children's and adults' responses to a particular HIV vaccine. Ten vertically HIV-infected children aged 4-16 years were immunized during antiretroviral therapy (ART). Another ten children were blindly recruited as controls. Both groups continued their antiretroviral treatment during and after vaccinations. Twelve chronically HIV-infected adults were vaccinated, followed by repeated structured therapy interruptions (STI) of their antiretroviral treatment. The adult group included four controls, receiving placebo vaccinations. The HIV-DNA vaccine was generally well tolerated, and no serious adverse events were registered in any group. In the HIV-infected children, an increased specific immune response to Gag and RT proteins was detected by antigen-specific lymphoproliferation. Moreover, the frequency of HIV-specific CD8+ T-cell lymphocytes releasing perforin was significantly higher in the vaccinees than the controls. In the HIV-infected adults, increased CD8+ T-cell responses to Gag, RT and viral protease peptides were detected. No augmentation of HIV-specific lymphoproliferative responses were detected in adults after vaccination. In conclusion, the HIV-DNA vaccine can elicit new HIV-specific cellular immune responses, particularly to Gag antigens, in both HIV-infected children and adults. Vaccinated children mounted transient new HIV-specific immune responses, including both CD4+ T-cell lymphoproliferation and late CD8+ T-cell responses. In the adult cohort, primarily CD8+ T-cell responses related to MHC class I alleles were noted. However, no clinical benefits with respect to viral load reduction were ascribable to the vaccinations alone. No severe adverse effects related to the vaccine were found in either cohort, and no virological failures or drug resistances were detected.

No MeSH data available.