Antonella Amendola

Safety and immunogenicity of influenza vaccination in individuals infected with HIV

Influenza can cause severe complications in HIV infected individuals leading to increases in hospitalisation and mortality. Vaccination is recommended for such individuals, but some studies reported that immunisation against influenza may stimulate an increase of HIV viral load and decrease of CD4+ cells count. A review of published studies, including our study carried out in HIV former drug addicts, indicates that vaccination against influenza is well tolerated in both children and adult individuals with HIV, but response to vaccination is lower than that observed in immunocompetent individuals. Most studies, including our own, show that vaccination does not induce significant changes in viral load and CD4+ cell counts. In studies reporting modifications of such parameters there is a general agreement that the increased viral replication is usually transient and unable to determine a clear, measurable progression of the underlying HIV disease. Therefore, vaccination against influenza can be safely administered to HIV infected people.

Influenza vaccination in patients with cirrhosis and in liver transplant recipients.

To assess the safety and immunogenicity of influenza vaccination, patients with cirrhosis undergoing treatment or not and liver transplant recipients under standard immunosuppression were vaccinated and followed up for 6 months. One month after vaccination, seroprotection rates and antibody GMTs against the three vaccine antigens were higher than baseline levels in all three patients groups. No differences in seroconversion and seroprotection rates were found within groups, but antibody GMTs against A/H1N1 and A/H3N2 strains were lower in liver transplant recipients than in patients with cirrhosis without treatment. No serious adverse events and no alteration of the liver function tests were observed. Patients with cirrhosis, including those under treatment, and liver transplant recipients benefit from influenza vaccination and can be safely immunized.

Safety and immunogenicity of 23-valent pneumococcal polysaccharide vaccine in HIV-1 infected former drug users

The immunogenicity of 23-valent pneumococcal polysaccharide vaccine was assessed in 57 HIV-1 infected former intravenous drug users and in 20 HIV-1 negative controls. The effect of vaccination on HIV-1 infection was studied in a subgroup of 38 patients, 60% of whom under highly active antiretroviral therapy (HAART). Antibody to capsular polysaccharides from Streptococcus pneumoniae serotypes 3, 4, 6B, 19F, 23 F, and changes in CD4+ count, HIV-1 RNA, proviral DNA and HIV-1 phenotype were measured in pre- and post-vaccination samples. Vaccinations were well-tolerated. The rate of responders was higher (P<0.05) in HIV-1 negative than in HIV-1 infected individuals. No difference in antibody response was found within HIV-1 infected patients stratified according to CD4+ counts. Post-vaccination antibody geometric mean concentrations (GMCs) to the five antigens were higher (P<0.05) than baseline in HIV-1 negative subjects, but not in HIV-1 positive individuals. Those with CD4+ >500 cells/mm(3) showed a significant increase of antibody against type 3 only. Immunisation caused no significant changes in CD4+ counts and in either plasma HIV-1 RNA nor proviral DNA levels. Pneumococcal vaccination does not induce virological or immunological deterioration in HIV infected patients, but the antibody response to a single dose of vaccine is poor.

Immunogenicity and safety of an adjuvanted influenza vaccine in patients with decompensated cirrhosis

The immunogenicity and tolerability of an adjuvanted trivalent influenza vaccine was evaluated in 20 patients with cirrhosis due to chronic HBV or HCV infections and eight healthy age matched controls. Seroconversion or a four-fold or greater increase in HI antibody titres to each antigen occurred in 75-85% of the patients and in 100% of the controls. One month after vaccination, the geometric mean antibody titres were significantly higher than baseline in both groups of vaccinees. A mild and transient erythema at the inoculation site was the only side effect for both groups. The results justify the use of an adjuvanted influenza vaccine, given as single-dose, in patients with advanced liver disease.

Rapid molecular evolution of human bocavirus revealed by Bayesian coalescent inference.

Human bocavirus (HBoV) is a linear single-stranded DNA virus belonging to the Parvoviridae family that has recently been isolated from the upper respiratory tract of children with acute respiratory infection. All of the strains observed so far segregate into two genotypes (1 and 2) with a low level of polymorphism. Given the recent description of the infection and the lack of epidemiological and molecular data, we estimated the viruss rates of molecular evolution and population dynamics. A dataset of forty-nine dated VP2 sequences, including also eight new isolates obtained from pharyngeal swabs of Italian patients with acute respiratory tract infections, was submitted to phylogenetic analysis. The model parameters, evolutionary rates and population dynamics were co-estimated using a Bayesian Markov Chain Monte Carlo approach, and site-specific positive and negative selection was also investigated. Recombination was investigated by seven different methods and one suspected recombinant strain was excluded from further analysis. The estimated mean evolutionary rate of HBoV was 8.6x10(-4)subs/site/year, and that of the 1st+2nd codon positions was more than 15 times less than that of the 3rd codon position. Viral population dynamics analysis revealed that the two known genotypes diverged recently (mean tMRCA: 24 years), and that the epidemic due to HBoV genotype 2 grew exponentially at a rate of 1.01year(-1). Selection analysis of the partial VP2 showed that 8.5% of sites were under significant negative pressure and the absence of positive selection. Our results show that, like other parvoviruses, HBoV is characterised by a rapid evolution. The low level of polymorphism is probably due to a relatively recent divergence between the circulating genotypes and strong purifying selection acting on viral antigens.

Phylogeny and population dynamics of respiratory syncytial virus (Rsv) A and B

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and young children. RSV is characterised by high variability, especially in the G glycoprotein, which may play a significant role in RSV pathogenicity by allowing immune evasion. To reconstruct the origin and phylodynamic history of RSV, we evaluated the genetic diversity and evolutionary dynamics of RSV A and RSV B isolated from children under 3 years old infected in Italy from 2006 to 2012. Phylogenetic analysis revealed that most of the RSV A sequences clustered with the NA1 genotype, and RSV B sequences were included in the Buenos Aires genotype. The mean evolutionary rates for RSV A and RSV B were estimated to be 2.1 × 10(-3) substitutions (subs)/site/year and 3.03 × 10(-3) subs/site/year, respectively. The time of most recent common ancestor for the tree root went back to the 1940s (95% highest posterior density-HPD: 1927-1951) for RSV A and the 1950s (95%HPD: 1951-1960) for RSV B. The RSV A Bayesian skyline plot (BSP) showed a decrease in transmission events ending in about 2005, when a sharp growth restored the original viral population size. RSV B BSP showed a similar trend. Site-specific selection analysis identified 10 codons under positive selection in RSV A sequences and only one site in RSV B sequences. Although RSV remains difficult to control due to its antigenic diversity, it is important to monitor changes in its coding sequences, to permit the identification of future epidemic strains and to implement vaccine and therapy strategies.

Epidemiological and clinical features of respiratory viral infections in hospitalized children during the circulation of influenza virus A(H1N1) 2009

Please cite this paper as: Zuccotti et al. (2011) Epidemiological and clinical features of respiratory viral infections in hospitalized children during the circulation of influenza virus A(H1N1) 2009. Influenza and Other Respiratory Viruses 5(6), e528–e534.

Response to 2009 pandemic and seasonal influenza vaccines co-administered to HIV-infected and HIV-uninfected former drug users living in a rehabilitation community in Italy.

BACKGROUND 2009 A(H1N1) pandemic influenza vaccination was recommended as a priority to essential workers and high-risk individuals, including HIV-infected patients and people living in communities. METHODS HIV-infected and HIV-uninfected former drug-users (18-60 years old) living in a rehabilitation community (San Patrignano, Italy) received one dose of a MF59-adjuvanted 2009 pandemic influenza vaccine and one dose of a 2009-2010 seasonal trivalent inactivated influenza vaccine (containing A/Brisbane/59/2007(H1N1), A/Brisbane/10/2007(H3N2), B/Brisbane/60/2008) simultaneously. Antibodies against each vaccine antigen were determined at the time of vaccination and one and six months post-vaccination by hemagglutination-inhibition test. RESULTS 49 HIV-infected and 60 HIV-uninfected subjects completed the study. Most (98%) HIV-infected participants were on antiretroviral treatment, the median CD4+ cell count was 350 (IQR 300)cells/μl and viremia was suppressed in 91.8% of cases. One month post-vaccination, no significant changes in immune-virological parameters were observed. One month post-vaccination, the immune responses to both pandemic and seasonal vaccine met the EMA-CPMP criteria for immunogenicity of influenza vaccines in both HIV-infected and HIV-uninfected subjects. No difference in vaccine responses was observed between the two groups. Six months after vaccination, the percentages of vaccinees with antibody titres ≥1:40 and antibody geometric mean titres significantly decreased in both groups. However, they were significantly lower in HIV-infected than in HIV-uninfected vaccinees. In subjects who had been primed to seasonal influenza the year before (through either vaccination or natural infection), levels of antibodies against 2009 A(H1N1) were higher than those measured in unprimed subjects, both one month and six months post-vaccination. CONCLUSIONS The co-administration of a single dose of 2009 pandemic MF59-adjuvanted influenza vaccine with a seasonal vaccine provided a protective immune response in both HIV-infected and HIV-uninfected individuals. Subjects who had been primed to seasonal influenza in the year preceding the pandemic had a more vigorous and long-lasting antibody response to 2009 pandemic vaccine.

Co-circulation of genetically distinct human metapneumovirus and human bocavirus strains in young children with respiratory tract infections in Italy†

The discovery of human Metapneumovirus (hMPV) and human Bocavirus (hBoV) identified the etiological causes of several cases of acute respiratory tract infections in children. This report describes the molecular epidemiology of hMPV and hBoV infections observed following viral surveillance of children hospitalized for acute respiratory tract infections in Milan, Italy. Pharyngeal swabs were collected from 240 children ≤3 years of age (130 males, 110 females; median age, 5.0 months; IQR, 2.0–12.5 months) and tested for respiratory viruses, including hMPV and hBoV, by molecular methods. hMPV‐RNA and hBoV‐DNA positive samples were characterized molecularly and a phylogenetical analysis was performed. PCR analysis identified 131/240 (54.6%) samples positive for at least one virus. The frequency of hMPV and hBoV infections was similar (8.3% and 12.1%, respectively). Both infections were associated with lower respiratory tract infections: hMPV was present as a single infectious agent in 7.2% of children with bronchiolitis, hBoV was associated with 18.5% of pediatric pneumonias and identified frequently as a single etiological agent. Genetically distinct hMPV and hBoV strains were identified in children examined with respiratory tract infections. Phylogenetic analysis showed an increased prevalence of hMPV genotype A (A2b sublineage) compared to genotype B (80% vs. 20%, respectively) and of the hBoV genotype St2 compared to genotype St1 (71.4% vs. 28.6%, respectively). Interestingly, a shift in hMPV infections resulting from A2 strains has been observed in recent years. In addition, the occurrence of recombination events between two hBoV strains with a breakpoint located in the VP1/VP2 region was identified. J. Med. Virol. 83:156–164, 2011.

Genetic drift influenza A(H3N2) virus hemagglutinin (HA) variants originated during the last pandemic turn out to be predominant in the 2011–2012 season in Northern Italy

Influenza A(H3N2) virus is once again the predominant strain after the 2009 pandemic. Its molecular epidemiology and phylogeny were investigated during the 2011-2012 season in Northern Italy. The epidemiological and virological influenza surveillance was carried out within the framework of the Italian Influenza Surveillance Network. The hemagglutinin (HA) gene of the A(H3N2) viruses detected was analyzed by means of a time-scaled phylogenetic approach. In Northern Italy, the 2011-2012 epidemic wave was sustained almost exclusively by influenza A(H3N2) viruses (87.2% of total influenza virus detections). The consultation rates for influenza-like illness (ILI) in the age group ≥65 years were 1.5 to 6-fold higher than those registered during the previous eight epidemics: A(H3N2) was the only virus identified in this group. The phylogenetic analysis of A(H3N2) viruses showed viruses belonging to the A/Victoria/208/2009 genetic clade, characterized by substitutions in HA antigenic sites with respect to the A/Perth/16/2009-like 2011-2012 vaccine strain. About one-third of analyzed sequences fell into group 6 and two thirds into group 3 (subdivided into 3A, 3B, and 3C). The time scale reconstruction of the phylogeny showed several independent introductions of A(H3N2) groups between summer and winter of 2011. However, the common origin of all the circulating A(H3N2) strains dated back to the 2009 pandemic period (November 2009). The time scale phylogenetic approach is of particular importance for the evaluation of the introduction and circulation of new variants in the area. Therefore, it should be implemented within the framework of influenza virological surveillance.