Novel S. aureus vaccine found safe, immunogenic

SAN DIEGO – A new vaccine was safe and prompted a durable antibody response against pathogenic strains of Staphylococcus aureus, based on findings from a phase I trial conducted in 408 healthy adults.

The investigational three-antigen vaccine, known as SA3Ag, uses antigens that have established pathogenicity, Dr. Michael Nissen reported at IDWeek. "There was a rapid and robust functional antibody response to the vaccine antigens after a single dose and in all age groups," he said.

Analyses further suggested that a second (booster) dose of vaccine had only a modest additional effect on the immune response at 12 months. "High GMTs [geometric mean titers] for each antigen at 6 months, when the booster was administered, probably limited the booster response at this time," speculated Dr. Nissen, who is an associate professor with the Queensland Paediatric Infectious Diseases Laboratory in Brisbane, Australia.

He noted that a similar investigational four-antigen S. aureus vaccine is currently being tested in a pair of clinical trials (NCT 01364571 and NCT 01643941).

"Because of the high health care burden of S. aureus infections, there is an unmet need for an effective S. aureus vaccine," he commented. The new SA3Ag vaccine "has been developed based on known S. aureus virulence factors, namely capsular polysaccharides CP5 and CP8, and clumping factor A." The former are proteins that allow the pathogen to evade phagocytosis, whereas the latter enables it to adhere to host tissues.

Study participants were healthy adults aged 18-85 years. In a first randomization, they were assigned to receive a low, medium, or high dose of the vaccine, or a placebo; in a second randomization 6 months later, the initial vaccine groups were assigned to receive the same dose again (a booster) or a placebo.

Immunogenicity results showed that about 1 month after initial vaccination, there was a rise in titers of functional antibodies against the three vaccine antigens across all dose levels and across all age groups, Dr. Nissen reported.

After a single dose of the vaccine, the titers gradually waned over 12 months, but still remained well above those at baseline and well above those seen with placebo.

The booster dose of vaccine at 6 months only modestly improved on immunogenicity against one of the antigens, clumping factor A.

"Here, there was again a gradual decline in GMTs [of all antigens] through 12 months, but GMTs remained high at 12 months following booster, and again they were above placebo," Dr. Nissen commented. "Therefore, the timing of the booster dose warrants further investigation."

In terms of local reactions to the vaccine, the most common was pain at the injection site. Rates of pain, swelling, and redness all increased with dose, and were all higher after the booster dose than after the initial dose. Local reactions prompted a discontinuation of booster dosing.

In terms of systemic reactions, the overall rate was similar to that with placebo across the three vaccine dose levels. New or worsening muscle pain was more common after the vaccine than after placebo.

Fever developed after vaccination in 1%-2% of participants, regardless of vaccine dose. There were no vaccine-related serious adverse events or deaths during the 12-month study period.

IDWeek is the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society

Dr. Nissen disclosed that he has received travel grants from Wyeth and Pfizer, and has been the principal investigator on trials sponsored by Abbott, Baxter, CSL Behring, and other companies.

SAN DIEGO – A new vaccine was safe and prompted a durable antibody response against pathogenic strains of Staphylococcus aureus, based on findings from a phase I trial conducted in 408 healthy adults.

The investigational three-antigen vaccine, known as SA3Ag, uses antigens that have established pathogenicity, Dr. Michael Nissen reported at IDWeek. "There was a rapid and robust functional antibody response to the vaccine antigens after a single dose and in all age groups," he said.

Analyses further suggested that a second (booster) dose of vaccine had only a modest additional effect on the immune response at 12 months. "High GMTs [geometric mean titers] for each antigen at 6 months, when the booster was administered, probably limited the booster response at this time," speculated Dr. Nissen, who is an associate professor with the Queensland Paediatric Infectious Diseases Laboratory in Brisbane, Australia.

He noted that a similar investigational four-antigen S. aureus vaccine is currently being tested in a pair of clinical trials (NCT 01364571 and NCT 01643941).

"Because of the high health care burden of S. aureus infections, there is an unmet need for an effective S. aureus vaccine," he commented. The new SA3Ag vaccine "has been developed based on known S. aureus virulence factors, namely capsular polysaccharides CP5 and CP8, and clumping factor A." The former are proteins that allow the pathogen to evade phagocytosis, whereas the latter enables it to adhere to host tissues.

Study participants were healthy adults aged 18-85 years. In a first randomization, they were assigned to receive a low, medium, or high dose of the vaccine, or a placebo; in a second randomization 6 months later, the initial vaccine groups were assigned to receive the same dose again (a booster) or a placebo.

Immunogenicity results showed that about 1 month after initial vaccination, there was a rise in titers of functional antibodies against the three vaccine antigens across all dose levels and across all age groups, Dr. Nissen reported.

After a single dose of the vaccine, the titers gradually waned over 12 months, but still remained well above those at baseline and well above those seen with placebo.

The booster dose of vaccine at 6 months only modestly improved on immunogenicity against one of the antigens, clumping factor A.

"Here, there was again a gradual decline in GMTs [of all antigens] through 12 months, but GMTs remained high at 12 months following booster, and again they were above placebo," Dr. Nissen commented. "Therefore, the timing of the booster dose warrants further investigation."

In terms of local reactions to the vaccine, the most common was pain at the injection site. Rates of pain, swelling, and redness all increased with dose, and were all higher after the booster dose than after the initial dose. Local reactions prompted a discontinuation of booster dosing.

In terms of systemic reactions, the overall rate was similar to that with placebo across the three vaccine dose levels. New or worsening muscle pain was more common after the vaccine than after placebo.

Fever developed after vaccination in 1%-2% of participants, regardless of vaccine dose. There were no vaccine-related serious adverse events or deaths during the 12-month study period.

IDWeek is the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society

Dr. Nissen disclosed that he has received travel grants from Wyeth and Pfizer, and has been the principal investigator on trials sponsored by Abbott, Baxter, CSL Behring, and other companies.

SAN DIEGO – A new vaccine was safe and prompted a durable antibody response against pathogenic strains of Staphylococcus aureus, based on findings from a phase I trial conducted in 408 healthy adults.

The investigational three-antigen vaccine, known as SA3Ag, uses antigens that have established pathogenicity, Dr. Michael Nissen reported at IDWeek. "There was a rapid and robust functional antibody response to the vaccine antigens after a single dose and in all age groups," he said.

Analyses further suggested that a second (booster) dose of vaccine had only a modest additional effect on the immune response at 12 months. "High GMTs [geometric mean titers] for each antigen at 6 months, when the booster was administered, probably limited the booster response at this time," speculated Dr. Nissen, who is an associate professor with the Queensland Paediatric Infectious Diseases Laboratory in Brisbane, Australia.

He noted that a similar investigational four-antigen S. aureus vaccine is currently being tested in a pair of clinical trials (NCT 01364571 and NCT 01643941).

"Because of the high health care burden of S. aureus infections, there is an unmet need for an effective S. aureus vaccine," he commented. The new SA3Ag vaccine "has been developed based on known S. aureus virulence factors, namely capsular polysaccharides CP5 and CP8, and clumping factor A." The former are proteins that allow the pathogen to evade phagocytosis, whereas the latter enables it to adhere to host tissues.

Study participants were healthy adults aged 18-85 years. In a first randomization, they were assigned to receive a low, medium, or high dose of the vaccine, or a placebo; in a second randomization 6 months later, the initial vaccine groups were assigned to receive the same dose again (a booster) or a placebo.

Immunogenicity results showed that about 1 month after initial vaccination, there was a rise in titers of functional antibodies against the three vaccine antigens across all dose levels and across all age groups, Dr. Nissen reported.

After a single dose of the vaccine, the titers gradually waned over 12 months, but still remained well above those at baseline and well above those seen with placebo.

The booster dose of vaccine at 6 months only modestly improved on immunogenicity against one of the antigens, clumping factor A.

"Here, there was again a gradual decline in GMTs [of all antigens] through 12 months, but GMTs remained high at 12 months following booster, and again they were above placebo," Dr. Nissen commented. "Therefore, the timing of the booster dose warrants further investigation."

In terms of local reactions to the vaccine, the most common was pain at the injection site. Rates of pain, swelling, and redness all increased with dose, and were all higher after the booster dose than after the initial dose. Local reactions prompted a discontinuation of booster dosing.

In terms of systemic reactions, the overall rate was similar to that with placebo across the three vaccine dose levels. New or worsening muscle pain was more common after the vaccine than after placebo.

Fever developed after vaccination in 1%-2% of participants, regardless of vaccine dose. There were no vaccine-related serious adverse events or deaths during the 12-month study period.

IDWeek is the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society

Dr. Nissen disclosed that he has received travel grants from Wyeth and Pfizer, and has been the principal investigator on trials sponsored by Abbott, Baxter, CSL Behring, and other companies.