CNPRC Study Leads to Meningococcal Vaccine Improvements

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CNPRC Study Leads to Meningococcal Vaccine Improvements

On February 12, 2015, CNPRC Affiliate Scientists Drs. Koen Van Rompay, Peter Beernink, and Dan Granoff announced important findings from a pilot project study conducted at the CNPRC on improving the effectiveness of the meningococcal vaccine for prevention of sepsis and meningitis caused by meningococci group B, a rare, and sometimes deadly, bacterial infection which accounts for one-third of the meningococcal meningitis cases in the U.S. (“A rhesus macaque immunogenicity model to investigate the effect of binding of complement factor H on meningococcal factor H binding protein vaccines” Granoff DM, et al, , Journal of Infectious Diseases, published ahead of print Feb 12, 2015, DOI: 10.1093/infdis/jiv081).

This life-threatening bacterial infection of the blood, brain, and spinal cord is spread from person-to-person, and the bacteria can be transmitted from a person who appears healthy. First-year college students, especially those living in residence halls, are at an increased risk for meningococcal disease (sepsis and/or meningitis).

The infections can cause shock, coma, and death within hours of the first symptoms. Even with proper treatment, 10–15% of people with meningococcal disease die. Of those that survive, as many as 20% suffer from some serious complication, such as loss of an arm or leg, brain damage, or permanent hearing loss.

Because college students are especially vulnerable to contracting meningococcal disease by living and studying in close quarters, vaccines are recommended for entering students. Meningococcal conjugate vaccines (Menactra or Menveo) offer protection against 4 groups of meningococcal bacteria, but do not cover serogroup B.

On February 23, 2015, a UC Davis student was diagnosed with meningococcal disease (group B). The student is receiving medical care and recovering.

In November 2014 and January 2015, the FDA approved two new Meningitis B vaccines (Trumenba® and Bexsero®) that will be available to prevent infection with the more common serotype B strain causing meningitis, and represent a significant step forward in helping prevent this devastating disease. Although not widely available, UCD Student Health is obtaining doses of these vaccines and be available to interested students.

However, Trumenba® and Bexsero® may not provide protection against all meningococcal serogroup B strains.

Recent outbreaks on other college campuses of serogroup B meningococcal disease led the FDA to accelerate the approval process for these vaccines. In 2013 and 2014, there were outbreaks at Princeton University and the University of California, Santa Barbara. 2015 has already seen campus infections from meningococcal serotype B, including sickening one student at UC Davis, and four University of Oregon students, killing one.

With the important goal of improving the efficacy of the serotype B meningococcal vaccine, Van Rompay, PhD, DVM, CNPRC; Beernink, PhD, Children’s Hospital Oakland Research Institute (CHORI); and Granoff, MD, Director, Center for Immunobiology and Vaccine Development CHORI, used the nonhuman primate model at the CNPRC to determine the effect of binding of a host protein (complement Factor H) to a vaccine antigen known as Factor H binding protein (FHbp). This antigen is a component of both serogroup B vaccines licensed in the U.S., including Bexsero®.

The research team recently discovered that a subset of rhesus macaques have complement Factor H that binds one of the most important antigens (Factor H binding protein, FHbp) in the serogroup B vaccine, and that binding of FH from these animals is similar to human FH.

Immunizing the infant nonhuman primates with Bexsero, they compared the responses of animals with high and low FH binding. The researchers were able to show a significant detrimental effect of FH binding on FHbp immunogenicity in the licensed vaccine, which has important implications for developing a second-generation vaccine with increased effectiveness.

The study has provided valuable information for development of improved FHbp vaccines for humans and highlights the value of this work in improving safety and immunogenicity against meningococcal disease.

Granoff DM, Costa I, Konar M, Giuntini S, Van Rompay KK, Beernink PT. Binding of Complement Factor H Decreases Protective Anti-FHbp Antibody Responses of Infant Rhesus Macaques Immunized with a Meningococcal Serogroup B Vaccine. J Infect Dis. 2015 Feb 12. pii: jiv081.

[Epub ahead of print]

 

2017-08-30T23:07:06+00:00 March 4th, 2015|Tags: , , , , |