Results support continued study of CMV vaccine

Micrograph showing
CMV infection

A vaccine designed to control cytomegalovirus (CMV) has produced favorable results in a phase 1 trial of healthy volunteers.

Investigators said the vaccine, known as Triplex, was well-tolerated at multiple dose levels.

The vaccine also generated “robust” and “durable” virus-specific immunity in subjects who were previously infected with CMV and those who were not.
 
The results of this study were published in Blood.

Triplex is a universal (non-HLA-restricted), recombinant modified vaccinia ankara viral vector vaccine engineered to induce a virus-specific T-cell response to 3 immuno-dominant proteins (UL83 [pp65], UL123 [IE1], and UL122 [IE2]) linked to CMV complications in the post-transplant setting.

Helocyte Inc. is developing the vaccine for control of CMV in recipients of allogeneic hematopoietic stem cell transplant (HSCT) and solid organ transplant.

This study was not funded by Helocyte. However, investigator Don J. Diamond, PhD, of City of Hope Comprehensive Cancer Center in Duarte, California is chair of Helocyte’s scientific advisory board and receives personal service fees from the company.

In this trial, Dr Diamond and his colleagues studied the response to Triplex in 24 healthy volunteers.

Subjects were divided into 3 groups of 8 receiving 3 different doses of the vaccine. The first dose level was 10xE7 plaque-forming units (pfu), the second was 5x10E7 pfu, and the third was 5x10E8 pfu.

The subjects received the vaccine in a volume of 1 mL by intramuscular injection in the upper arm and an identical booster injection 28 days later.

Safety

The investigators said Triplex was well tolerated in most subjects at all dose levels. There were no dose-limiting toxicities and no serious adverse events attributed to the vaccine.

One subject experienced a grade 3 injection site adverse event (erythema), which resolved in 1 day without treatment. In addition, there were 3 mild-to-moderate cutaneous reactions.

The investigators said the most common systemic reaction was mild-to-moderate flu-like symptoms. Most subjects in the highest dose group experienced these symptoms, as did a few subjects from the lower dose groups. All of these events were transient, self-limiting, and resolved.

Immunogenicity

The investigators reported “robust, functional, and durable” expansion of CMV-specific T cells after Triplex vaccination, in subjects with and without prior CMV infection.

At day 42, subjects had experienced a significant increase in pp65-specific T cells from baseline. The P values were 0.0003 for pp65-specific CD137+ CD8+ T cells and 0.001 for CD137+ CD4+ T cells.

Expansion remained above baseline levels until at least day 360 for pp65-specific CD137+ CD8+ T cells and at least until day 482 for pp65-specific CD137+ CD4+ T cells.

IE1-exon4- and IE2-exon5-specific T-cell expansions occurred as well, although the increase from baseline was not significant for IE1-exon4-specific T cells.

The median concentrations of IE2-exon5-specific T cells had increased significantly from baseline at day 42—for both CD137+ CD8+ T cells (P=0.014) and CD137+ CD4+ T cells (P=0.003).

The investigators noted that there was no significant difference in the responses to all 3 CMV libraries according to Triplex dose level, previous smallpox vaccination, or CMV-serostatus.

Next, the team found that Triplex vaccination induced significant expansion of pp65-specific IFN-γ+ CD8+ T cells. They said this suggests the vaccine was able to expand a functional subset of CMV-specific T cells, even in the absence of CMV viremia.

The median concentration of pp65-specific IFN-γ + CD8+ T cells increased significantly from baseline to day 28 (P=0.024), day 56 (P=0.003), day 100 (P=0.011), and day 360 (P=0.085).

There was no significant increase for pp65-specific IFN-γ + CD4+ T cells, IE1-exon4-specific IFN-γ+ T cells, or IE2-exon5-specific IFN-γ + T cells.

The investigators also said the Triplex vaccine induced significant vaccinia-specific T-cell increases by day 42 (P=0.0005), with an estimated decline to pre-vaccination levels at day 274.

These data supported the initiation of an ongoing phase 2 trial in which investigators are evaluating Triplex in patients undergoing allogeneic HSCT (NCT02506933).

“After years of work, it is very gratifying that we are making advancements in helping people worldwide achieve better health outcomes after a transplant procedure,” said Dr Diamond, who led the team that developed Triplex.

“Furthermore, Triplex’s favorable safety and immunogenicity may make the vaccine an ideal therapeutic platform to combat significant complications in many disease areas, like solid organ transplant and glioblastoma.”

Micrograph showing
CMV infection

A vaccine designed to control cytomegalovirus (CMV) has produced favorable results in a phase 1 trial of healthy volunteers.

Investigators said the vaccine, known as Triplex, was well-tolerated at multiple dose levels.

The vaccine also generated “robust” and “durable” virus-specific immunity in subjects who were previously infected with CMV and those who were not.
 
The results of this study were published in Blood.

Triplex is a universal (non-HLA-restricted), recombinant modified vaccinia ankara viral vector vaccine engineered to induce a virus-specific T-cell response to 3 immuno-dominant proteins (UL83 [pp65], UL123 [IE1], and UL122 [IE2]) linked to CMV complications in the post-transplant setting.

Helocyte Inc. is developing the vaccine for control of CMV in recipients of allogeneic hematopoietic stem cell transplant (HSCT) and solid organ transplant.

This study was not funded by Helocyte. However, investigator Don J. Diamond, PhD, of City of Hope Comprehensive Cancer Center in Duarte, California is chair of Helocyte’s scientific advisory board and receives personal service fees from the company.

In this trial, Dr Diamond and his colleagues studied the response to Triplex in 24 healthy volunteers.

Subjects were divided into 3 groups of 8 receiving 3 different doses of the vaccine. The first dose level was 10xE7 plaque-forming units (pfu), the second was 5x10E7 pfu, and the third was 5x10E8 pfu.

The subjects received the vaccine in a volume of 1 mL by intramuscular injection in the upper arm and an identical booster injection 28 days later.

Safety

The investigators said Triplex was well tolerated in most subjects at all dose levels. There were no dose-limiting toxicities and no serious adverse events attributed to the vaccine.

One subject experienced a grade 3 injection site adverse event (erythema), which resolved in 1 day without treatment. In addition, there were 3 mild-to-moderate cutaneous reactions.

The investigators said the most common systemic reaction was mild-to-moderate flu-like symptoms. Most subjects in the highest dose group experienced these symptoms, as did a few subjects from the lower dose groups. All of these events were transient, self-limiting, and resolved.

Immunogenicity

The investigators reported “robust, functional, and durable” expansion of CMV-specific T cells after Triplex vaccination, in subjects with and without prior CMV infection.

At day 42, subjects had experienced a significant increase in pp65-specific T cells from baseline. The P values were 0.0003 for pp65-specific CD137+ CD8+ T cells and 0.001 for CD137+ CD4+ T cells.

Expansion remained above baseline levels until at least day 360 for pp65-specific CD137+ CD8+ T cells and at least until day 482 for pp65-specific CD137+ CD4+ T cells.

IE1-exon4- and IE2-exon5-specific T-cell expansions occurred as well, although the increase from baseline was not significant for IE1-exon4-specific T cells.

The median concentrations of IE2-exon5-specific T cells had increased significantly from baseline at day 42—for both CD137+ CD8+ T cells (P=0.014) and CD137+ CD4+ T cells (P=0.003).

The investigators noted that there was no significant difference in the responses to all 3 CMV libraries according to Triplex dose level, previous smallpox vaccination, or CMV-serostatus.

Next, the team found that Triplex vaccination induced significant expansion of pp65-specific IFN-γ+ CD8+ T cells. They said this suggests the vaccine was able to expand a functional subset of CMV-specific T cells, even in the absence of CMV viremia.

The median concentration of pp65-specific IFN-γ + CD8+ T cells increased significantly from baseline to day 28 (P=0.024), day 56 (P=0.003), day 100 (P=0.011), and day 360 (P=0.085).

There was no significant increase for pp65-specific IFN-γ + CD4+ T cells, IE1-exon4-specific IFN-γ+ T cells, or IE2-exon5-specific IFN-γ + T cells.

The investigators also said the Triplex vaccine induced significant vaccinia-specific T-cell increases by day 42 (P=0.0005), with an estimated decline to pre-vaccination levels at day 274.

These data supported the initiation of an ongoing phase 2 trial in which investigators are evaluating Triplex in patients undergoing allogeneic HSCT (NCT02506933).

“After years of work, it is very gratifying that we are making advancements in helping people worldwide achieve better health outcomes after a transplant procedure,” said Dr Diamond, who led the team that developed Triplex.

“Furthermore, Triplex’s favorable safety and immunogenicity may make the vaccine an ideal therapeutic platform to combat significant complications in many disease areas, like solid organ transplant and glioblastoma.”

Micrograph showing
CMV infection

A vaccine designed to control cytomegalovirus (CMV) has produced favorable results in a phase 1 trial of healthy volunteers.

Investigators said the vaccine, known as Triplex, was well-tolerated at multiple dose levels.

The vaccine also generated “robust” and “durable” virus-specific immunity in subjects who were previously infected with CMV and those who were not.
 
The results of this study were published in Blood.

Triplex is a universal (non-HLA-restricted), recombinant modified vaccinia ankara viral vector vaccine engineered to induce a virus-specific T-cell response to 3 immuno-dominant proteins (UL83 [pp65], UL123 [IE1], and UL122 [IE2]) linked to CMV complications in the post-transplant setting.

Helocyte Inc. is developing the vaccine for control of CMV in recipients of allogeneic hematopoietic stem cell transplant (HSCT) and solid organ transplant.

This study was not funded by Helocyte. However, investigator Don J. Diamond, PhD, of City of Hope Comprehensive Cancer Center in Duarte, California is chair of Helocyte’s scientific advisory board and receives personal service fees from the company.

In this trial, Dr Diamond and his colleagues studied the response to Triplex in 24 healthy volunteers.

Subjects were divided into 3 groups of 8 receiving 3 different doses of the vaccine. The first dose level was 10xE7 plaque-forming units (pfu), the second was 5x10E7 pfu, and the third was 5x10E8 pfu.

The subjects received the vaccine in a volume of 1 mL by intramuscular injection in the upper arm and an identical booster injection 28 days later.

Safety

The investigators said Triplex was well tolerated in most subjects at all dose levels. There were no dose-limiting toxicities and no serious adverse events attributed to the vaccine.

One subject experienced a grade 3 injection site adverse event (erythema), which resolved in 1 day without treatment. In addition, there were 3 mild-to-moderate cutaneous reactions.

The investigators said the most common systemic reaction was mild-to-moderate flu-like symptoms. Most subjects in the highest dose group experienced these symptoms, as did a few subjects from the lower dose groups. All of these events were transient, self-limiting, and resolved.

Immunogenicity

The investigators reported “robust, functional, and durable” expansion of CMV-specific T cells after Triplex vaccination, in subjects with and without prior CMV infection.

At day 42, subjects had experienced a significant increase in pp65-specific T cells from baseline. The P values were 0.0003 for pp65-specific CD137+ CD8+ T cells and 0.001 for CD137+ CD4+ T cells.

Expansion remained above baseline levels until at least day 360 for pp65-specific CD137+ CD8+ T cells and at least until day 482 for pp65-specific CD137+ CD4+ T cells.

IE1-exon4- and IE2-exon5-specific T-cell expansions occurred as well, although the increase from baseline was not significant for IE1-exon4-specific T cells.

The median concentrations of IE2-exon5-specific T cells had increased significantly from baseline at day 42—for both CD137+ CD8+ T cells (P=0.014) and CD137+ CD4+ T cells (P=0.003).

The investigators noted that there was no significant difference in the responses to all 3 CMV libraries according to Triplex dose level, previous smallpox vaccination, or CMV-serostatus.

Next, the team found that Triplex vaccination induced significant expansion of pp65-specific IFN-γ+ CD8+ T cells. They said this suggests the vaccine was able to expand a functional subset of CMV-specific T cells, even in the absence of CMV viremia.

The median concentration of pp65-specific IFN-γ + CD8+ T cells increased significantly from baseline to day 28 (P=0.024), day 56 (P=0.003), day 100 (P=0.011), and day 360 (P=0.085).

There was no significant increase for pp65-specific IFN-γ + CD4+ T cells, IE1-exon4-specific IFN-γ+ T cells, or IE2-exon5-specific IFN-γ + T cells.

The investigators also said the Triplex vaccine induced significant vaccinia-specific T-cell increases by day 42 (P=0.0005), with an estimated decline to pre-vaccination levels at day 274.

These data supported the initiation of an ongoing phase 2 trial in which investigators are evaluating Triplex in patients undergoing allogeneic HSCT (NCT02506933).

“After years of work, it is very gratifying that we are making advancements in helping people worldwide achieve better health outcomes after a transplant procedure,” said Dr Diamond, who led the team that developed Triplex.

“Furthermore, Triplex’s favorable safety and immunogenicity may make the vaccine an ideal therapeutic platform to combat significant complications in many disease areas, like solid organ transplant and glioblastoma.”