Short-term and long-term antibody response by mice after immunization against Neisseria meningitidis B or diphtheria toxoid

Abstract

Serogroup B Neisseria meningitidis (MenB) is a major cause of invasive disease in early childhood worldwide. The only MenB vaccine available in Brazil was produced in Cuba and has shown unsatisfactory efficacy when used to immunize millions of children in Brazil. In the present study, we compared the specific functional antibody responses evoked by the Cuban MenB vaccine with a standard vaccine against diphtheria (DTP: diphtheria, tetanus, pertussis) after primary immunization and boosting of mice. The peak of bactericidal and opsonic antibody titers to MenB and of neutralizing antibodies to diphtheria toxoid (DT) was reached after triple immunization with the MenB vaccine or DTP vaccine, respectively. However, 4 months after immunization, protective DT antibody levels were present in all DTP-vaccinated mice but in only 20% of the mice immunized against MenB. After 6 months of primary immunization, about 70% of animals still had protective neutralizing DT antibodies, but none had significant bactericidal antibodies to MenB. The booster doses of DTP or MenB vaccines produced a significant antibody recall response, suggesting that both vaccines were able to generate and maintain memory B cells during the period studied (6 months post-triple immunization). Therefore, due to the short duration of serological memory induced by the MenB vaccine (VA-MENGOC-BC H vaccine), its use should be restricted to outbreaks of meningococcal disease.

Recombinant Neisseria surface protein A is a potential vaccine candidate against Neisseria meningitides serogroup B

“…meningitidis is the pathogen of epidemic encephalomyelitis and predominantly affects children between the ages of six months to two years, who are particularly susceptible due to their underdeveloped immune systems. The mortality rate is high following infection (13,14). Currently, among all N. meningitidis groups, the capsular polysaccharide in N. meningitidis serogroup B has a similar structure to that of the human tissue, A B Figure 5.…”

“…Despite the fact that capsular polysaccharide occurs on the surface of N. meningitidis serogroup B, it is likely to trigger a cross reaction, as its structure is similar to mammalian gangliosides. Therefore, vaccines that mimic the capsular polysaccharide of N. meningitidis serogroup B are not suitable for development due to the risk of autoimmune disease (13,14).…”

Construction and protective immunogenicity of DNA vaccine pNMB0315 against Neisseria�meningitidis serogroup B

“…The mortality rate of meningococcemia is up to 40% as meningococcemia is more severe than general meningococcal diseases. (2,6). CPS-based vaccines are available and are used for the prevention of infection by N. meningitides serogroups A, C, W135 and Y infections, and the development of an effective vaccine against NMB is important for the prevention and control of the disease (8).…”

“…Neisseria meningitidis (N. meningitidis) is a Gram-negative microorganism and a major causative agent of severe sepsis and meningitis (1), both of which may lead to mortality in children and young adults within h, although effective antibiotics are available (2,3). N. meningitidis causes meningococcal diseases in ~500,000 people annually worldwide, mainly affecting children between the ages of 3 and 48 months, followed by adolescents (4), and although drug treatments such as penicillin are available, 10-15% of children and adolescents succumb to infection.…”

“…CPS-based vaccines have been developed and used successfully to prevent the invasive meningococcal disease that may be caused by serogroups A, C, W135 and Y (7). However, the CPS of N. meningitidis serogroup B (NMB) is an α 2-8 -linked polysialic acid that resembles a molecule that is present on the surface of human tissues, thus making a NMB CPS-based vaccine poorly immunogenic, as well as presenting a possible cause of autoimmunity (2,7,8).…”