Novel vaccine safety issues and areas that would benefit from further research.

Vaccine licensure requires a very high safety standard and vaccines routinely used are very safe. Vaccine safety monitoring prelicensure and postlicensure enables continual assessment to ensure the benefits outweigh the risks and, when safety problems arise, they are quickly identified, characterised and further problems prevented when possible. We review five vaccine safety case studies: (1) dengue vaccine and enhanced dengue disease, (2) pandemic influenza vaccine and narcolepsy, (3) rotavirus vaccine and intussusception, (4) human papillomavirus vaccine and postural orthostatic tachycardia syndrome and complex regional pain syndrome, and (5) RTS,S/adjuvant system 01 malaria vaccine and meningitis, cerebral malaria, female mortality and rebound severe malaria. These case studies were selected because they are recent and varied in the vaccine safety challenges they elucidate. Bringing these case studies together, we develop lessons learned that can be useful for addressing some of the potential safety issues that will inevitably arise with new vaccines.

Post-marketing safety surveillance for inactivated and live-attenuated Japanese encephalitis vaccines in China, 2008-2013.

INTRODUCTION: Two types of Japanese encephalitis (JE) vaccines, inactivated JE vaccine (JE-I) and live-attenuated JE vaccine (JE-L), are available and used in China. In particular, one JE-L, produced by a domestic manufacturer in China, was prequalified by WHO in 2013. We assessed the safety of JE vaccines in China during 2008-2013 using the Chinese National Adverse Events Following Immunization Information System (CNAEFIS) data. METHODS: We retrieved AEFI reporting data about JE vaccines from CNAEFIS, 2008-2013, examined demographic characteristics of AEFI cases, and used administrative data on vaccine doses as denominator to calculate and compare crude reporting rates. We also used disproportionality reporting analysis between JE-I and JE-L to assess potential safety signals. RESULTS: A total of 34,879 AEFIs related with JE-I and JE-L were reported, with a ratio of male to female as 1.3:1; 361 (1.0%) cases were classified as serious. JE vaccines were administered concurrently with one or more other vaccines in 13,592 (39.0%) of cases. The overall AEFI reporting rates were 214.4 per million vaccination doses for JE-L and 176.9 for JE-I (rate ratio [RR]: 1.2, 95% confidence interval [CI]: 1.1-1.3) in 2010-2013. Febrile convulsions (FC) following JE-I was found as a signal of disproportionate reporting (SDR). However, there was no significant difference between the reporting rates of FC of JE-I and JE-L (0.3 per million vaccination doses for JE-L, 0.4 for JE-I, p=0.05). CONCLUSIONS: While our analysis did not find apparent safety concern of JE vaccines in China, further study should consider JE-I vaccines and febrile convulsion, and taking more sensitive methods to detect signals.

Immunogenicity and reactogenicity of 23-valent pneumococcal polysaccharide vaccine among pregnant Filipino women and placental transfer of antibodies.

This randomized, controlled study among pregnant women evaluated the prevaccination distribution of anti-pneumococcal (Pnc) antibodies (Ab), the immunogenicity and reactogenicity of Pnc polysaccharide vaccine, and transplacental transfer of Ab. The Pnc vaccine group (N=106) received Pnc PS vaccine, Hemophilus influenzae type b conjugate vaccine and tetanus toxoid; the control group (N=54) received tetanus toxoid only. Sera and cord blood were assayed for anti-pnc Ab using enzyme immunoassay. In the Pnc vaccine group, anti-Pnc Ab rose by 3- to 9-fold and was significantly higher in cord blood. In evaluating Pnc conjugate vaccines, the concentration of 0.35 microg/ml is suggested as the protective threshold against invasive disease. Around 90% of mothers had this level pre-vaccination. Considering the decay of passively acquired Ab and the growth of the infant, an Ab level in cord blood of at least 4.4 microg/ml is needed if infants are to be protected up to 4 months of age. Cord blood anti-Pnc Ab was above this level in 60% and 10% of the Pnc vaccine and control groups, respectively. Maternal immunization with Pnc polysaccharide vaccine can provide prolonged protection through passively acquired Ab.