Cytomegalovirus (CMV)

1st CMV Vaccine Candidate To Launch Phase 2 Study

Don Hackett — Tue, 11 Feb 2020 14:23:27 +0000

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A Massachusetts based biotechnology company announced that the Phase 2 clinical study dose-confirmation study of its messenger RNA vaccine against cytomegalovirus (CMV) is enrolling ahead of plan with data now expected in the third quarter of 2020.

Moderna Inc.’s CMV vaccine candidate mRNA-1647 is the first mRNA vaccine for an infectious disease to enter a Phase 2 study.

The Company is actively preparing for a Phase 3 pivotal study, which will evaluate the prevention of primary CMV infection in a population that includes women of childbearing age.

“I am pleased with the continued progress of our late-stage CMV vaccine program as we prepare for a pivotal Phase 3 study and commercial readiness,” said Stéphane Bancel, Moderna’s Chief Executive Officer, in a related press release.

The potential advantages of an mRNA approach to prophylactic vaccines include the ability to mimic natural infection to stimulate a more potent immune response, combining multiple mRNAs into a single vaccine, rapid discovery to respond to emerging pandemic threats and manufacturing agility derived from the platform nature of mRNA vaccine design and production, says the company.

“I am proud of the team’s ability to rapidly respond to the ongoing public health crisis posed by the novel coronavirus and to be working with the National Institutes of Health and Coalition for Epidemic Preparedness Innovations.”

On January 24, 2020, Moderna announced the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases, would collaborate with Moderna to design a coronavirus messenger RNA (mRNA) vaccine candidate.

Moderna’s mRNA-1273 is an mRNA vaccine candidate against the novel coronavirus encoding for the viral Spike (S) protein.

The S protein complex is necessary for membrane fusion and host cell infection and has been the target of vaccines against the coronaviruses responsible for Middle Eastern Respiratory Syndrome and Severe Acute Respiratory Syndrome.

The first clinical batch of mRNA-1273, including fill and finishing of vials, was completed on February 7, 2020. This mRNA vaccine was designed and manufactured in 25 days and is undergoing analytical testing prior to release to the NIH for use in their planned Phase 1 clinical trial in the U.S.

This is good news since there are no approved vaccines specific to the 2019-nCoV, as of February 11, 2020.

Moderna has built a fully integrated manufacturing plant in Norwood, MA which enables the promise of the technology platform.

Moderna is advancing messenger RNA science to create a new class of transformative medicines for patients. Headquartered in Cambridge, Mass., Moderna currently has strategic alliances for development programs with AstraZeneca, Plc., Merck, Inc., as well as the Defense Advanced Research Projects Agency, an agency of the U.S. Department of Defense; the Biomedical Advanced Research and Development Authority, a division of the Office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services.

Vaccine Development news is published by Precision Vaccinations.

Sub Title:

Moderna CMV vaccine candidate mRNA-1647 is the first mRNA vaccine for an infectious disease to enter a Phase 2 study

References:

Moderna Announces Progress in Prophylactic Vaccines Modality with CMV Vaccine Phase 2 Study Data Now Expected in Third Quarter 2

mRNA-1647 Cytomegalovirus Vaccine

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Cytomegalovirus Vaccine Candidate Announces Very Positive News

Don Hackett — Fri, 10 Jan 2020 18:38:23 +0000

Reviewer:

Danielle Reiter, RN

Robert Carlson, MD

A biotechnology company based in Massachusetts announced positive 7-month interim safety and immunogenicity data after the 3rd and final vaccination in the Phase 1 study of its investigational cytomegalovirus (CMV) vaccine candidate, mRNA-1647.

The findings published by Moderna, Inc. on January 9, 2020, builds on the previously reported 3-month interim analysis during September 2019.

“Prevention of CMV in women of childbearing age is an urgent unmet need. mRNA-1647 is the first mRNA vaccine for an infectious disease to enter a Phase 2 clinical trial,” said Stéphane Bancel, Moderna’s CEO, in a press release.

This is important news since there is currently no approved vaccine for the prevention of CMV infection.

The mRNA-1647 vaccine comprises 6 mRNAs encoding 2 antigens in 1 vaccine and is designed to protect against CMV infection.

Of the 6 mRNAs, 5 encode the subunits of the CMV pentamer complex and 1 mRNA encodes the glycoprotein B (gB) protein, both of which are highly immunogenic.

Both pentamer and gB proteins are essential for CMV to enter epithelial cells, which is the first step in CMV infection.

mRNA-1647 is designed to produce an immune response to both pentamer and gB antigens to prevent CMV infection.

CMV is a common pathogen and member of the herpesvirus family, which includes herpes simplex virus types 1 & 2, varicella-zoster virus, and Epstein-Barr virus.

For most people, CMV infection is not a serious health problem, said the Centers for Disease Control and Prevention (CDC) in May 2019.

However, certain groups are at high-risk for serious complications from CMV infection:

Infants infected in utero (congenital CMV infection)

Very low birth weight and premature infants

People with compromised immune systems.

Congenital CMV infection results when infected mothers transmit the virus to their unborn child, and it is the leading infectious cause of birth defects in the United States with approximately 25,000 newborns in the U.S. infected every year.

Birth defects occur in approximately 20 percent of infected babies and include neurodevelopmental disabilities such as hearing loss, vision impairment, varying degrees of learning disability and decreased muscle strength and coordination.

CMV is spread through saliva, breastmilk, mucus, and urine and is common in healthy babies and toddlers; as a result, young children can be a major source of infection for pregnant women, and others, says the CDC.

The 2nd interim analysis of the Phase 1 trial reports safety and immunogenicity of the first three dose levels (30, 90 and 180 µg) through seven months (one month after the third vaccination) and the highest dose level (300 µg) through three months (one month after the second vaccination).

Neutralizing antibody titers were assessed in two assays utilizing epithelial cells and fibroblasts, which measure the immune response to pentamer and gB antigens, respectively.

Safety data were consistent with those reported at the three-month interim analysis. The vaccine was generally well-tolerated and there were no vaccine-related serious adverse events (SAEs).

The most common solicited local adverse reaction (AR) across all vaccinations was injection site pain (54-100% of a given treatment group). The most common solicited systemic ARs reported overall were headache, fatigue, myalgia, and chills.

Fever was reported in 0-55% of CMV-seronegative treatment groups and in 8-67% of CMV-seropositive treatment groups.

The most common Grade 3 solicited ARs were in CMV-seropositive participants and were fatigue (0-27% of a given treatment group), chills (0-27% of a given treatment group) and fever (0-33% of a given treatment group).

In general, the highest solicited systemic AR rates were reported after the second vaccination, were more frequent in the CMV-seropositive compared to the CMV-seronegative group, and tended to correlate to dose.

As reported in the previous interim analysis, one related Grade 4 adverse event (AE) has been observed, which was an isolated lab finding of elevated partial thromboplastin time (PTT), which was elevated at baseline (Grade 1) and self-resolved on the next lab test with no associated clinical findings.

In the CMV-seronegative group at 7 months:

Neutralizing antibody titers continued to increase after the third vaccination in both epithelial cell and fibroblast assays.

Neutralizing antibody titers against epithelial cell infection was greater than 10-fold higher than CMV-seropositive baseline titers at the 90 and 180 µg dose levels after the third vaccination, compared to 3-fold to 5-fold higher after the second vaccination.

Neutralizing antibody titers against fibroblast infection increased to 1.4-fold higher than CMV-seropositive baseline titers at the 90 and 180 µg dose levels after the third vaccination, compared to titers that were comparable to CMV-seropositive baseline titers after the second vaccination.

In the CMV-seropositive group at 7 months:

Neutralizing antibody titers continued to increase after the third vaccination in both epithelial cell and fibroblast assays.

Third vaccination boosted neutralizing antibody titers against epithelial cell infection to levels of 22-fold to 40-fold over baseline across treatment groups, compared to 10-fold to 19-fold over baseline after the second vaccination.

Third vaccination boosted neutralizing antibody titers against fibroblast infection to levels of 4-fold to 6-fold over baseline across treatment groups, compared to 2-fold to 4-fold over baseline after the second vaccination.

Samples from a subset of CMV-seronegative participants from the 30, 90 and 180 µg dose levels demonstrated T-cell reactivity against the gB antigen at all doses. Pentamer-based T-cell assays remain in development.

This interim analysis also reports the first data from the 300 µg dose level through 3 months (one month after the second vaccination), which continued to show consistent dose-dependent increases in neutralizing antibodies against epithelial cell infection and against fibroblast infection in both CMV-seronegative and CMV-seropositive participants.

Safety and tolerability at the 300 µg dose level were comparable to that observed at the 180 µg dose level.

“These data are significant because they show that after a 3rd dose, mRNA-1647 continues to increase durable immune responses that exceed the levels of those with natural CMV infection,” said Tal Zaks, M.D., Ph.D., chief medical officer at Moderna.

“There is no approved vaccine to prevent CMV infection despite repeated attempts over the last 50 years.”

“With mRNA-1647, which encodes for both the pentamer and gB antigens, we believe we can significantly reduce the burden of CMV infection, including in women of childbearing age, concluded Dr. Zaks in the press release.

A 12-month interim analysis is planned, which will report safety and immunogenicity through six months after the third vaccination.

Separately, Moderna said the 1st participant has been dosed in the randomized, observer-blind, placebo-controlled, dose-confirmation Phase 2 study, which will investigate the safety and immunogenicity of mRNA-1647 in approximately 252 healthy adults in the U.S. at three dose levels (50, 100 and 150 μg) in both CMV-seronegative and CMV-seropositive participants administered in a 3-dose vaccination schedule (0, 2 and 6 months).

This Phase 2 study will test the intended Phase 3 formulation, which contains the same proprietary lipid nanoparticle (LNP) used in the Phase 1 study. The first interim analysis will evaluate safety and immunogenicity at three months (one month after the second vaccination) and is intended to inform Phase 3 dose selection. mRNA-1647 is the first mRNA vaccine for an infectious disease to enter a Phase 2 clinical trial.

With the seven-month Phase 1 data and the launch of the Phase 2 study, the Company is actively preparing for a global randomized, observer-blind, placebo-controlled Phase 3 pivotal study to evaluate the efficacy of mRNA-1647 against primary CMV infection.

Moderna has solicited and received Type C meeting feedback from the FDA on the preliminary design of the pivotal trial, which will evaluate the prevention of primary CMV infection in a population that includes women of childbearing age.

Preclinical data previously published in Vaccine showed that vaccination with mRNA-1647 in animal models elicited potent and durable neutralizing antibody titers.

Moderna is advancing messenger RNA (mRNA) science to create a new class of transformative medicines for patients. To learn more visit ModernATX.

Cytomegalovirus Vaccine news published by Precision Vaccinations.

Sub Title:

Moderna mRNA-1647 vaccine continues to increase durable immune responses after third dose exceeding natural cytomegalovirus infection levels

References:

Moderna Announces Additional Positive Phase 1 Data from Cytomegalovirus (CMV) Vaccine (mRNA-1647) and First Participant Dosed

Moderna Announces Positive Interim Results from Phase 1 Cytomegalovirus (CMV) Vaccine (mRNA-1647) Study and Progress Toward

CDC: Cytomegalovirus (CMV) and Congenital CMV Infection

mRNA-1647 Cytomegalovirus Vaccine

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Thursday, April 15, 2021 - 05:30

$3.9 Million Dollar Grant Awarded For Cytomegalovirus Vaccine Development

Don Hackett — Wed, 25 Sep 2019 14:03:16 +0000

Reviewer:

Robert Carlson, MD

Danielle Reiter, RN

A researcher at the University of Minnesota (U of M) Medical School has been awarded a National Institutes of Health (NIH) grant for $3.9 million dollars to conduct research studies of novel vaccine strategies for cytomegalovirus (CMV).

Currently, there is not a CMV vaccine licensed for human use.

This announcement published on September 4, 2019, is good news since CMV is the most common infection that causes birth defects and disabilities in babies in the United States.

Nationally, about 1 baby in 100 is born with CMV. Infants that are CMV infected in utero could be born with birth defects and disabilities.

Out of the 7 billion people in the world, it’s estimated that more than 5 billion have been, or will be, infected with CMV.

Furthermore, the National Academy of Medicine has identified a CMV vaccine as being the ‘highest public health priority for any new vaccine.’

“CMV has coevolved with people since the advent of humankind,” said Mark R. Schleiss, M.D., Professor, Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, U of M, in a press release.

“A vaccine for CMV would be a huge public breakthrough and save the healthcare systems billions of dollars every year.”

Most people who contract CMV sometime after birth have no symptoms and don’t even know they have it. The virus is transmitted through bodily fluids.

“You aren’t going to get it riding the Green Line,” Dr. Schleiss said.

Schleiss concluded saying that ‘young women who have children can get CMV from their toddlers in daycare. One of the most common ways infants can contract the virus is from breastfeeding.’

Cytomegalovirus (CMV) vaccine news

CMV is a common pathogen and member of the herpesvirus family. CMV is a common virus that infects people of all ages, says the Centers for Disease Control and Prevention (CDC).

Using a guinea pig model of congenital CMV infection, Dr. Schleiss and his team intend to examine the use of recombinant techniques to modify the immune modulation genes encoded by CMV that impair the protective immune response.

This research will be working toward a better understanding of how to prevent congenital transmission of infection.

Previous research had shown that within a single individual HCMV has high genome (genetic) diversity, leading to theories that HCMV has a high mutation rate.

However, instead, the frequent occurrence of mixed-infections caused by genetically different HCMV strains leads to findings of high genome diversity within an individual.

Additional research collaborators include Dr. Craig Bierle and Drs. Adam Geballe (University of Washington) and Mike McVoy (Medical College of Virginia).

The University of Minnesota Medical School is at the forefront of learning and discovery, transforming medical care and educating the next generation of physicians. Learn how the University of Minnesota is innovating all aspects of medicine.

CMV news published by Precision Vaccinations

Sub Title:

Minnesota CMV vaccine researchers receive NIH funding

References:

University of Minnesota: Mark R. Schleiss, MD

U of M Researcher Awarded $3.9 Million NIH Grant for CMV Vaccine Studies

University researcher awarded $3.9 million grant to study herpes virus vaccine

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Cytomegalovirus Vaccine Candidate Heads to Phase 2 Study

Don Hackett — Thu, 12 Sep 2019 13:41:22 +0000

Reviewer:

Robert Carlson, MD

Danielle Reiter, RN

A Massacutists based biotech company announced positive data from the 3-month interim analysis of safety and immunogenicity of the Phase 1 clinical study of its investigational vaccine mRNA-1647, which treats cytomegalovirus (CMV).

Moderna Inc.’s mRNA-1647 is a 2-antigen vaccine designed to protect against CMV infection. It combines 6 mRNAs in a proprietary lipid nanoparticle (LNP) in a single vial and encodes for 2 immuno-dominant proteins of CMV.

This phase 1 study reported:

In seronegative participants

A dose-related increase in neutralizing antibody titers was observed in both epithelial cell and fibroblast assays.

In epithelial cells, after the second vaccination, neutralizing antibody titers were 3 to 5 times higher than CMV-seropositive baseline titers at the 90 and 180 µg dose levels.

In fibroblasts, after the second vaccination, neutralizing antibody titers were equivalent to CMV-seropositive baseline titers at the 90 and 180 µg dose levels.

For the 12 sentinel participants who received mRNA-1647 under an earlier arm of the protocol (Phase A) and who received three doses (at 0, 2 and 6 months), neutralizing antibody titers were further boosted at 7 months and were sustained at or above CMV-seropositive baseline levels for at least 12 months.

In seropositive participants

A dose-related increase in neutralizing antibody titers was observed in both epithelial cell and fibroblast assays.

In epithelial cells, the second vaccination boosted neutralizing antibody titers to a level of 10-fold to 19-fold baseline titers in all dose groups.

In fibroblasts, the second vaccination boosted neutralizing antibody titers to a level of 2-fold to 4-fold baseline titers in all dose groups.

Based on this new data, Moderna Inc., said in a September 12, 2019, press release, ‘it is advancing mRNA-1647 to a dose-confirmation Phase 2 study in the near term.’

And, ‘preparation has also begun for a pivotal Phase 3 study designed to evaluate the efficacy of mRNA-1647 against primary CMV infection.’

This is good news since CMV is the most common infectious cause of birth defects in the USA, and there is not a preventive vaccine available today.

“The Moderna research, development and manufacturing teams have been working to ensure this program can transition in the near term to a dose-confirmation Phase 2 study, while also preparing for a pivotal Phase 3 study with the goal of ensuring commercial readiness,” said Stéphane Bancel, Moderna’s chief executive officer.

The Phase 2 study will test the intended Phase 3 formulation, which contains the same proprietary LNP used in this Phase 1 study.

“I am very encouraged by the ability of mRNA-1647 to induce high levels of durable immune responses that can reach or exceed the levels generated by natural CMV infection,” said Tal Zaks, M.D., Ph.D., chief medical officer at Moderna.

“We recognize there is an urgent need for a preventative vaccine against congenital CMV and will be advancing mRNA-1647 into a Phase 2 study in the near term to confirm the appropriate dose, while we plan for a pivotal Phase 3 study.”

“Cytomegalovirus is the leading infectious cause of birth defects, and there is a great need for a vaccine that blocks transmission of the virus from the mother to the fetus,” said Sallie Permar, M.D., Ph.D., associate dean of physician-scientist development and professor of pediatrics, immunology, and molecular genetics and microbiology at Duke Medical School.

“These interim data are exciting because mRNA-1647 has shown the ability to induce immune responses in seronegative individuals that are greater than what is seen in those naturally infected with CMV, which is important in that natural immunity is not completely protective against congenital CMV transmission.”

CMV is a common pathogen and member of the herpesvirus family. CMV is a common virus that infects people of all ages. Over half of adults by age 40 have been infected with CMV, says the Centers for Disease Control and Prevention (CDC).

Most people infected with CMV show no signs or symptoms.

But, when a baby is born with a CMV infection, it is called congenital CMV.

About 1 out of every 200 babies is born with congenital CMV infection. About 20 percent of babies with congenital CMV infection will have long-term health problems.

Congenital CMV infection results when infected mothers transmit the virus to their unborn child.

CMV is spread through saliva, mucus, and urine and is common in healthy babies and toddlers; as a result, young children can be a major source of infection for pregnant women, particularly mothers, daycare workers, preschool teachers, therapists, and nurses, said the Company.

Moderna, Inc. is advancing messenger RNA (mRNA) science to create a new class of transformative medicines for patients. mRNA medicines are designed to direct the body’s cells to produce intracellular, membrane or secreted proteins that can have a therapeutic or preventive benefit and have the potential to address a broad spectrum of diseases.

Published by Precision Vaccinations

Sub Title:

Moderna mRNA-1647 2-antigen vaccine is designed to protect against CMV infection

References:

Moderna Announces Positive Interim Results from Phase 1 Cytomegalovirus (CMV) Vaccine (mRNA-1647) Study and Progress Toward

CDC: Cytomegalovirus (CMV) and Congenital CMV Infection

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CMV Vaccine Candidate Found Safe and Well-Tolerated

Don Hackett — Thu, 10 May 2018 20:26:57 +0000

Reviewer:

Robert Carlson, MD

Danielle Reiter, RN

Shane Kyral, PharmD

An innovative vaccine manufacturer announced positive final top-line results from the Phase 1 study of VBI-1501, the company’s prophylactic cytomegalovirus (CMV) vaccine candidate.

CMV is a common virus that infects people of all ages. Over half of adults by age 40 have been infected with CMV, says the Centers for Disease Control and Prevention.

Once CMV is in a person’s body, it stays there for life and can reactivate. Most people infected with CMV show no signs or symptoms.

However, CMV infection can cause serious health problems for people with weakened immune systems, as well as babies infected with the virus before they are born (congenital CMV).

Each year, approximately 5,000 U.S. infants will develop permanent problems due to CMV, which can include deafness, blindness, and developmental delays.

CMV affects more live births than Down syndrome or fetal alcohol syndrome, making it a key public health priority and a strong candidate for recommended universal vaccination and reimbursement.

VBI-1501 was developed using the company’s proprietary enveloped virus-like particle (eVLP) technology and presents a modified form of the glycoprotein B (gB) found on CMV.

The final Phase 1 study results demonstrated that VBI-1501 was safe and well-tolerated at all doses.

The highest dose of VBI-1501, 2.0μg, elicited protective CMV-neutralizing antibodies against fibroblast cell infection in 100% of subjects after the third vaccination, inducing titers comparable to those observed in patients protected as a result of natural infection.

Neutralizing antibodies against epithelial cell infection were also seen in 31% of subjects receiving the same dose.

Final immunogenicity data from VBI’s Phase 1 study included gB antibody binding titers and neutralizing antibody seroconversion in both fibroblast and epithelial cells, two cell types CMV infects that are widely used to gauge the potency of CMV vaccine candidates.

Joanne Langley, M.D., an Associate Director with the Canadian Center for Vaccinology located at Dalhousie University, and Principal Investigator of the study further commented, “The safety profile of this vaccine is such that there is little concern about evaluating VBI-1501 at higher doses in the next stage of clinical development.”

“With the functional activity we’ve seen, even at a low dose, these results are incredibly encouraging.”

This study was a Phase 1 randomized, observer-blind, placebo-controlled study to evaluate the safety, tolerability, and immunogenicity of VBI’s preventative CMV vaccine in healthy adults.

The study enrolled 125 CMV-negative participants, aged 18-40 years, who were randomized into five arms to receive various dose levels of a modified form of the CMV antigen gB, gB-G, with or without the adjuvant alum, or placebo:

0.5μg of gB-G content with alum (VBI-1501A 0.5μg)
1.0μg of gB-G content with alum (VBI-1501A 1.0μg)
1.0μg of gB-G content without alum (VBI-1501 1.0μg)
2.0μg of gB-G content with alum (VBI-1501A 2.0μg)
Placebo

Participants were vaccinated at zero, two, and six months.

Additional information, including a detailed description of the study design, eligibility criteria, and investigator sites, is available at ClinicalTrials.gov using identifier NCT02826798.

VBI Vaccines Inc. (“VBI”) is a commercial-stage biopharmaceutical company developing a next generation of vaccines to address unmet needs in infectious disease and immuno-oncology.

Sub Title:

VBI Vaccines Phase 1 study of VBI-1501 elicited protective cytomegalovirus-neutralizing antibodies against fibroblast cell infection in 100% of subjects after the third vaccination

References:

Cytomegalovirus (CMV) and Congenital CMV Infection

VBI Vaccines Announces Positive Final Phase 1 Study Results of Preventative CMV Vaccine

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