Impacts on influenza A(H1N1)pdm09 infection from cross-protection of seasonal trivalent influenza vaccines and A(H1N1)pdm09 vaccines: Systematic review and meta-analyses
Highlights
► Systematic reviews of cross-protection of TIVs & A(H1N1)pdm09 vaccine effectiveness. ► TIVs provided moderate cross-protection against confirmed A(H1N1)pdm09 illness. ► A(H1N1)pdm09 vaccines were highly effective against confirmed illness.
Introduction
A novel influenza virus, A(H1N1)pdm09, was detected in April 2009 [1] and the World Health Organization (WHO) declared the first influenza pandemic of the 21st century 2 months later [2]. Cross-reacting antibodies against this virus were found in the elderly [3], [4], [5] while most of the younger population were at risk of the infection based on serology [6].
There are data suggesting that previous seasonal trivalent influenza vaccines (TIVs) could produce some cross-protection [7], [8], [9], [10], [11], [12]. However, a protective benefit was questioned by some health authorities [13], [14], and brought into doubt by other studies that showed no significant protection [13], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27] or even increased risk [28], [29] of acquiring the virus. Due to the substantial heterogeneities in study results, study designs, and quality of studies, it was difficult to draw a clear conclusion.
On the other hand, after the A(H1N1)pdm09 vaccines were widely distributed, the immunogenicity and short-term safety of various formulations of novel A(H1N1)pdm09 vaccines were clearly demonstrated [30]. Nevertheless, their clinical benefit in preventing disease has not yet been addressed in a systematic way. As several studies [8], [17], [24], [25], [26], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41] have already reported on vaccine effectiveness (VE), and given the important medical and health-policy implications, there is a need for a meaningful systematic review and meta-analyses to assess both the cross-protection of TIVs against A(H1N1)pdm09 infection and the VE of monovalent A(H1N1)pdm09 vaccines. Using the “Population, Intervention, Comparison, and Outcome” framework, our study was in human populations, given either TIVs or monovalent A(H1N1)pdm09 vaccines, comparing with subjects who were not vaccinated with TIV or A(H1N1)pdm09 vaccines and assessing the vaccine effect on preventing A(H1N1)pdm09 disease.
Section snippets
Literature search and selection criteria
Database searches, conducted by a medical librarian (CK), were limited to Humans. No date limits were applied, however, the searches were naturally limited to items reported beginning in 2009 when the pandemic commenced. The last search was undertaken on 18th July 2011. A copy of the full strategy used in OVID Medline is available if required. The searches were undertaken in Ovid MEDLINE (1948 to July Week 1 2011) and Ovid EMBASE (1980 to 2011 Week 28), The Cochrane Library databases – Cochrane
Results
Of the 2178 studies initially retrieved, we identified 34 relevant studies addressing either cross-protection of TIV and/or direct protection of A(H1N1)pdm09 vaccines against either confirmed A(H1N1)pdm09 infection or other relevant endpoints. Two publications reported the same study [20], [48] so we included 33 publications which covered 3,019,399 subjects (Fig. 1 and Table 2). The study by Skowronski published in 2010 [29] was divided into three case–control studies and one cohort study in
Discussion
Our systematic review and meta-analyses demonstrate moderate cross-protection of seasonal influenza vaccines of 34–38% against laboratory-confirmed 2009 A(H1N1)pdm09 illness (based on eight case–control studies [7], [10], [17], [23], [24], [25], [26], [29] and one RCT [12]) and perhaps protection from hospitalisation too (one case–control study) [11]. This finding is consistent with observations from a previous pandemic. No publication bias was identified [50].
No association was detected
Conclusions
Through our systematic review and meta-analyses, we are able to inform governments, academics, medical practitioners and others that, during the delay in A(H1N1)pdm09 vaccine production, seasonal influenza vaccination seemed to provide moderate protection of the population, perhaps less so initially but more later, and furthermore that, although limited by observational study design, the A(H1N1)pdm09 vaccines were generally highly effective against laboratory confirmed A(H1N1)pdm09 illness.
Acknowledgement
We gratefully thank Donna Armstrong for assistance with the literature review.
Contributors: All authors contributed significantly to the study. JKY and RB were involved in all phases of the study. CK conducted the literature search. MYKC assisted JKY in data extraction. PR provided the results of one unpublished RCT [12]. JKY led the statistical analysis. JKY and MYKC did the assessment of risk of bias. JKY, MYKC, GK, LH, PR and RB wrote the manuscript. Funding: None. Conflict of interest
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