By Roberto Fernandez-Larsson and Kristen Jill Kresge
Phase I Trial of ADMVA Vaccine Begins in New York
The Aaron Diamond AIDS Research Center (ADARC) in New York City recently began enrolling volunteers for a preventive AIDS vaccine trial in partnership with The Rockefeller University and the International AIDS Vaccine Initiative. The Phase I safety and immunogenicty study of the Center’s vaccine, ADMVA, will enroll 48 healthy volunteers in New York City and Rochester, New York. The candidate vaccine, ADMVA, contains the env/gag-poland nef-tat fusion genes of HIV and uses a modified vaccinia Ankara (MVA) viral vector. The HIV genes contained in the candidate vaccine are derived from subtype C, prevalent in China, India, and Africa.
“The epidemic in China is burgeoning and the only hope for some people is a vaccine. We are particularly excited about the MVA vector,” said Sarah Schlesinger of ADARC. If results from this trial show the vaccine is safe and effective at inducing an immune response then further clinical trials will be initiated in other regions of the world. For more information visit www.adarc.org
India’s First AIDS Vaccine Trial Starts
India began enrolling volunteers for the country’s first preventive AIDS vaccine trial in February. The phase I safety study will evaluate the immunogenicity of a vaccine manufactured by the Seattle based company Targeted Genetics. The National AIDS Research Institute in Pune is conducting the trial, in partnership with the Indian Council of Medical Research (ICMR) and the International AIDS vaccine Initiative.
Thirty volunteers will receive a single immunization with the recombinant adeno-associated vaccine, known as tgAAC09, a recombinant vaccine made from HIV genes enclosed in the capsid of Adeno-Associated Virus (AAV). The AAV vector was developed by Phil Johnson, formerly at the Columbus Children’s Research Institute and currently with the Children’s Hospital of Philadelphia, and is now licensed to Targeted Genetics. The candidate vaccine contains HIV’s gag, protease, and RT sequences and is designed to stimulate both a cellular and humoral immune response to HIV clade C. Preclinical animal studies conducted by Targeted Genetics found that tgAAC09 induced strong cytotoxic T-cell and antibody responses to HIV.
The vaccine candidate is being tested in a joint Phase I clinical trial in Germany, Belgium and now India. The start of the study was hailed as an important advancement in a country with the second largest number of people living with HIV/AIDS in the world. “With this first trial, Indian scientists are making an important contribution that will bring the world a step closer to an AIDS vaccine,” said N.K. Ganguly, Director General of ICMR.
This vaccine trial also emphasizes the critical value of partnerships between governments, private companies, and public organizations in the process of finding an effective AIDS vaccine.
NIAID Begins Enrolling Volunteers for Phase IIb Study of Merck’s Vaccine
Enrollment began in December at sites in the US and Canada for a Phase IIb proof of concept study on Merck & Co’s lead AIDS vaccine candidate, MRKAd5. This efficacy trial will involve 1,500 high risk volunteers and is being conducted in collaboration with the HIV Vaccine Trials Network (HVTN) and the National Institutes of Allergies and Infectious Diseases. Enrollment will continue in the coming months in Peru, the Dominican Republic, Haiti, Puerto Rico,and Australia.
MRKAd5 is a trivalent vaccine that includes gag, pol, and nef genes from subtype B HIV and utilizes a human adenovirus serotype 5 (Ad5) vector. The trial will test two primary endpoints: the ability of the vaccine candidate to provide protection against HIV infection or control viral load in those newly infected. Volunteers in the trial will receive three vaccinations over a sixmonth period. Anyone who is incidentally infected with HIV during the course of the trial will be followed to see how the vaccine influences viral load and disease progression.
In earlier studies with the Ad5 construct, immune responses were weaker in individuals who had pre-existing immunity due to previous infection with the naturally circulating adenovirus serotype. This trial will exclude volunteers with an Ad5 neutralizing antibody titer over 1:200, to maximize responses to the HIV antigens.
Previous studies of this vaccine generated strong cellular immune responses in humans. If the immune response in this trial is sufficient to prevent infection with HIV a larger efficacy trial will be required before the vaccine is submitted to the FDA for approval.