Post-marketing study on the safety of a meningococcal group A, C bivalent polysaccharide conjugate vaccine

To the Editor

Meningococcal meningitis is a serious infectious disease, and significant complications, such as quadriplegia and mental retardation, may develop in 10–20% of individuals who survive this disease. Infants between the ages of 3 and 12 mo are the main age group susceptible to infection with meningococcal meningitis, and the administration of a safe and effective meningococcal vaccine is the most important preventative measure for halting the spread of this disease.^1,2 Currently, epidemic strains of meningitis in China are transitioning from group A to group C.³ In recent years, a bivalent A+C meningococcal vaccine has been successfully developed and used among the general Chinese population. In this study, we conducted a post-marketing assessment of the safety of this vaccine.

This study examined the freeze-dried meningococcal group A+C bivalent polysaccharide conjugate vaccine (Walvax BioTech Co., Ltd.), which was administered at doses of 20 µg/0.5 ml/vial. The following vaccination procedures were adopted. Children between 5 and 12 mo of age were vaccinated at 5, 6, and 9 mo of age, receiving a total of 3 doses of vaccine. Children between 13 and 23 mo of age were inoculated twice, at months 0 and 1; in other words, these children received 2 doses of the vaccine, with a 1-mo interval between the 2 inoculations. Children between 2 and 5 y of age received 1 dose of the vaccine. The study subjects were healthy children, as verified by physical examinations and medical history inquiries. Both active and passive surveillance schemes were employed. In the active surveillance of this study, the study subjects were divided into the 3 aforementioned age-based groups (5–12 mo, 13–23 mo, and 2–5 y), and 50 or more individuals were randomly selected from each group as subjects for monitoring adverse reactions. In the passive surveillance of this study, a minimum of 10 000 individuals were randomly selected from the children of 5 mo to 5 y old who had been admitted to standardized vaccination clinics in Guangzhou to receive the bivalent meningococcal vaccine, and adverse reactions were monitored among these selected passive surveillance subjects. The study period was from October 2011 to September 2012. Systemic and local post-vaccination reactions were assessed based on the Clinical Study Guidelines for the Evaluation of Adverse Effects of Prophylactic Vaccines (published by the China State Food and Drug Administration, 2005). The ethics committee of GZCDC reviewed and approved this protocol.

This study included a total of 10 609 healthy children. In particular, 253 vaccinated children with an average age of 2.50 ± 1.17 y were subjected to active surveillance. None of the infants and children younger than 24 mo of age in the active surveillance population exhibited any local or systemic adverse reactions within 30 min or 3 d after receiving any of the 3 doses of vaccine. Among the 193 children between 2 and 5 y of age who received 1 dose of the vaccine, 7 children (3.627%) experienced mild or local adverse reactions after the inoculation. In particular, 4 (2.073%) of these 7 children developed local induration, 1 child (0.495%) experienced local skin redness, 1 child (0.518%) exhibited local swelling of the skin, and 1 child (0.518%) experienced a mild post-vaccination systemic reaction that manifested as fatigue and weakness. Children of different genders exhibited no statistically significant differences in adverse reactions (P > 0.05).

The average age of the 10 356 children subjected to passive surveillance was 1.73 ± 1.19 y; specifically, there were 5379, 1701, and 3276 children aged from 5 to 12 mo, 13 to 23 mo and 2 to 5 y, respectively. Among the children subjected to passive surveillance, there were 19 reported cases (0.183%) of mild local reactions around the injection site; these reactions primarily manifested as induration, redness or swelling, and none of these adverse reactions affected the children’s mobility. There were 9 cases of systemic post-vaccination reactions, including 7 cases of fever (which was mild or moderate in 5 of these 7 cases [71.4%]), and all of the children who experienced systemic reactions recovered after receiving treatment in hospital. The passive surveillance results are summarized in Table 1. Among the children who were subjected to passive surveillance, there was a statistically significant difference in adverse reactions between children of different genders (P < 0.05).

Table 1. The passive surveillance activity of the meningococcal group A+C bivalent polysaccharide conjugate vaccine.

	5–12 mo	13–23 mo	2–5 y	Total
Local reaction
Pain	0	0	0	0
Mucocutaneous	1 (0.019)	0	0	1 (0.010)
Hardening	5 (0.093)	2 (0.118)	0	7 (0.068)
Redness	5 (0.093)	2 (0.118)	1 (0.031)	8 (0.077)
Swelling	0	1 (0.059)	2 (0.061)	3 (0.029)
Rash	0	0	0	0
Pruritus	0	0	0	0
Total	11 (0.204)	5 (0.294)	3 (0.092)	19 (0.183)
General reaction
Fever
37.1–37.5	1 (0.019)	0	0	1 (0.010)
37.6–39.0	4 (0.074)	0	0	4 (0.039)
>39.0	2 (0.037)	0	0	2 (0.019)
Allergic reaction	0	0	0	0
Headache	0	0	0	0
Fatigue	0	0	0	0
Anorexia	0	0	0	0
Nausea and vomiting	2 (0.037)	0	0	2 (0.019)
Diarrhea	0	0	0	0
In total	9 (0.167)	0	0	9 (0.087)

*Numbers in parentheses indicate the rate of occurrence (%).

We observed a lower rate of adverse reactions to the examined vaccine in comparison to a previous post-marketing examination of a conjugate meningococcal vaccine in another country.⁴ This discrepancy may reflect differences in national definitions of adverse reactions but could also have been caused by the underestimation of certain mild adverse reactions in the current study. Overall, the results of this study revealed that the examined conjugate A+C meningococcal vaccine exhibited excellent safety during its widespread use among the Chinese population. The excellent immunogenicity and safety of this vaccine indicate that it is appropriate to promote the administration of this vaccine to children and adolescents.

10.4161/hv.26347