Meningococcal A conjugate vaccine during pregnancy
The Committee was presented with results from an open label observational evaluation of the safety of a meningococcal A conjugate vaccine in pregnancy (MenAfriVac, manufactured by the Serum Institute of India), conducted in Ghana. The vaccine is a lyophilized group A conjugate vaccine developed under the Meningitis Vaccine Project.3 It contains PsA10 µg, TT conjugate 10–33 µg, aluminium phosphate adjuvant 0.3mg Al3+ and thiomersal 0.01%, in each 0.5 ml dose.
The GACVS had been following the vaccine from its initial Phase 1 and 2/3 clinical trials with just over 1100 subjects, through to licensure and the first mass immunization campaigns conducted in early adopter countries.4 By the time of the last update, in June 2011, over 50 million doses had been administered. At each update, the GACVS continued to be reassured of its ongoing safety while recommending specific actions be taken to help ensure continued safety vigilance and attention to key aspects of safety. As is common, clinical trials during vaccine development and licensure did not target pregnant women, however inadvertent vaccination in pregnancy throughout the early phases had not revealed any concerns.
GACVS supported WHO’s technical guidance5 that MenAfriVac should be offered to pregnant and lactating women from the African meningitis belt during any stage of pregnancy or lactation, while recommending that a plan be developed to follow up women in antenatal or obstetric clinics, and to monitor pregnancy outcomes by making appropriate comparisons with unvaccinated pregnant women.6
This study was developed in response to those recommendations. The Navrongo Health Research Centre, Ghana, is part of the INDEPTH network that collects continuous longitudinal demographic and health data and outcomes within its populations. In the surveillance area (covering 2 districts – Kassena-Nankana East and Kassena-Nankana West), >156 000 individuals are part of this demographic surveillance, and receive visits by study teams about 3–4 times per year to update their demographic and health status. A mass vaccination campaign was held in Ghana between 9 and 19 October 2012, targeting individuals between 1 and 29 years of age including pregnant women. While pregnancy was not considered a contraindication during this campaign given the benefit of vaccination, some pregnant women elected not to receive the vaccine. Given the participation of the districts in the INDEPTH network, this provided an opportunity to evaluate the safety of the meningococcal A vaccine by comparing the rates of pregnancy-related outcomes in vaccine recipients, with rates among unvaccinated pregnant women. In addition, a second age and season matched historical control group was assembled to document pregnancy outcomes in a time period before the immunization campaign. Outcomes included overall maternal, fetal and neonatal mortality, overall rates of spontaneous abortions, still births, perinatal deaths, prematurity, low birth weight, small for gestational age, and rates of caesarean section.
A total of 1730 pregnant women were vaccinated during the campaign, while 919 pregnant women elected not to be vaccinated. A total of 3551 pregnant women were in the historical unvaccinated control group. Comparing the outcomes, there was no significant difference in any of the pre-specified outcomes between women who had received the meningococcal A conjugate vaccine and those who had not, either in the concurrent or historical comparison groups. Mean birth weights were over or near 2900g in each group, and gestational age over 37 weeks. Rates of miscarriage and stillbirth were 1.8% in the vaccinated and 2.2% in both control groups, with prematurity 3.1% among the concurrent controls, 3.6% in the vaccinated and 5.6% among the comparison controls.
The Committee noted the quality of this study and its reassuring results. It highlighted the potential for this study methodology to examine the safety of vaccines in mass immunization contexts, especially in outcomes as complex as pregnancy. Previous attempts to study pregnancy outcomes have been less robust. Some details were more difficult to ascertain in this study, including reasons for spontaneous abortion, impact of vaccination during lactation and other factors that the demographic survey questions had not collected. However, future studies could be planned that would include additional variables added to the survey visits to address these questions.
Given that mass immunization campaigns have been staggered and another 100 million individuals are in line for vaccination over the next 2 years, opportunities for additional evaluation of meningococcal A conjugate vaccine in pregnancy will be available. This may include an opportunity to evaluate the vaccine’s safety during lactation. This present study was conducted using existing infrastructure in the Navrongo Health Research Centre and thus may provide a powerful tool in these evaluations.
Overall, in the almost 4 years since MenAfriVac was rolled out in the first mass campaigns, and beginning even earlier with the clinical trials, no concerns have been identified regarding its use in pregnancy. As with other inactivated vaccines, neither pregnancy nor lactation are contraindications for vaccination in situations of increased disease risk. Given the emerging evidence of the effectiveness of this meningococcal A conjugate vaccine in controlling disease in the countries of the meningitis belt in Africa, more permissive language in the package insert may be warranted.
3 See http://www.meningvax.org/
4 See No. 30, 2011, pp. 321–324.
6 See No. 30, 2010, pp. 285–291.