Mariella Neri

Antibody responses and HIV-1 viral load in HIV-1-seropositive subjects immunised with either the MF59-adjuvanted influenza vaccine or a conventional non-adjuvanted subunit vaccine during highly active antiretroviral therapy.

OBJECTIVE To study immunological and virological parameters in HIV-1-seropositive adults treated with highly active antiretroviral therapy (HAART) for at least 7 months after immunisation with MF59-adjuvanted (FLUAD, Chiron, Siena, Italy) or with non-adjuvanted (AGRIPPAL, Chiron) trivalent influenza vaccine. DESIGN Blood samples, collected before and after vaccination, were analysed for the presence of antibodies against the vaccine antigens, for number of CD4+ T lymphocytes and HIV-1 RNA levels. RESULTS Forty-four volunteers received FLUAD and 40 AGRIPPAL influenza vaccine. Thirty days after vaccination both adjuvanted and non-adjuvanted vaccines induced significant increases of anti-influenza virus antibodies. However, antibody titres found in volunteers receiving adjuvanted vaccine were in general significantly higher when compared with those found in the non-adjuvanted vaccine group. The requirements of the European Commission of influenza vaccine for a non-elderly adult population were always met by recipients of the adjuvanted vaccine, even in those with the lowest CD4+ cell counts (<200 cells/mmc). The subjects receiving the non-adjuvanted vaccine failed to met these requirements. The CD4+ T lymphocytes and plasma HIV-1 RNA levels remained stable in the long term, both in people receiving adjuvanted or non-adjuvanted vaccine. CONCLUSION MF59-adjuvanted influenza induced a significant higher immune responses as compared with conventional vaccine in HIV-seropositive HAART-treated patients. Both vaccines were safe regarding HIV RNA viral replication and loss of CD4+ T lymphocytes.

Immunogenicity of influenza vaccine (1993–1994 winter season) in HIV-seropositive and -seronegative ex-intravenous drug users

The humoral response (haemagglutination inhibiting antibodies) to trivalent split influenza vaccine for the 1993-94 winter season (A/Beijing/32/92 (H3N2), A/Singapore/6/86 (H1N1) and B/Panama/45/90) was evaluated in a group of young HIV-seropositive ex-intravenous heroin users and compared with responses measured in HIV-seronegative individuals with a similar history. HIV-negative volunteers showed an overall positive response suggesting that previous heroin use did not influence their humoral response to influenza vaccine. Comparable results were obtained in HIV-positive subjects with CD4+ lymphocyte counts > 500 microliters-1, whereas impaired reactivity was found in HIV-positive volunteers with CD4+ counts < 500 microliters-1. Booster vaccination did not increase antibody levels in any of the groups studied, although the data did not exclude a positive influence of a second vaccine dose on persistence of antibody at 120 days after the first dose. No significant changes were observed in p24 antigenemia levels in HIV-positive individuals after vaccination.

Immunogenicity of trivalent subunit and split influenza vaccines (1989–90 winter season) in volunteers of different groups of age

Trivalent split or subunit influenza vaccines [A/Shangai/11/87 (H3N2), A/Singapore/6/86 (H1N1) and B/Yamagata/16/88] recommended for the 1989-90 winter season and licensed in Italy, were administered to 149 volunteers of three different age groups (elderly, middle-aged and young). Antibody production was determined in pre- and postvaccination sera by haemagglutinin inhibition test and the results were evaluated as protection and response rates. The split vaccine was more immunogenic than the subunit preparation, especially against the B virus strain. Age had no obvious impact on the degree of responsiveness to vaccination.

Cross-reactive antibodies in middle-aged and elderly volunteers after MF59-adjuvanted subunit trivalent influenza vaccine against B viruses of the B/Victoria or B/Yamagata lineages

This study evaluated whether MF59-adjuvanted subunit trivalent influenza vaccine for the 2003/04 winter season (A/Moscow/10/99, H3N2; A/New Caledonia/20/99, H1N1; B/Hong Kong/330/01) would confer protection against mismatched and frequently co-circulating variants of influenza B/Victoria- and B/Yamagata-like virus strains. Haemagglutination inhibiting (HI) antibodies were measured in middle-aged and elderly volunteers against the homologous B/Victoria-like vaccine strain (B/Hong Kong/330/01) and against mismatched B/Victoria-like (B/Malaysia/2506/04) and B/Yamagata-like (B/Singapore/379/99 and B/Shanghai/361/02) strains. Immunization induced significant increases in the amounts of HI antibodies against all influenza B strains under investigation. However, the responses against the heterologous B/Shanghai/361/02 virus did not reach the desirable values of seroprotection. An age-dependent decline of the responses was found for B/Victoria-like antigens, but not for B/Yamagata-like strains. Although further studies are needed, our data support the recommendation of including influenza B viruses of the B/Victoria and B/Yamagata lineages in the future influenza vaccine preparations.

Effects of Repeated Annual Influenza Vaccination on Antibody Responses against Unchanged Vaccine Antigens in Elderly Frail Institutionalized Volunteers

Background: Concern about the possibility that annually repeated influenza immunizationmayinduce a lower antibody response than first vaccination. Objective: To ascertain the cumulative effects of yearly vaccination on serological response to unaltered vaccine antigens in the elderly. Methods: The haemagglutination-inhibiting (HI) antibody response was examined in 158 elderly institutionalized frail volunteers subdivided in 3 groups according to the sequential winters in which each subject received a trivalent inactivated influenza vaccine. The study, conducted over 5 consecutive winters (from 1998/99 to 2002/03), reports the antibody response only for sequential years (2 or 3) in which the vaccine strain examined was not altered. Results: Significant increases in the values of HI antibody titres were observed after vaccination in each year examined against the different influenza vaccine strains used, except against B antigen in the second of the 3 winters studied (1999/00). The antibody responses found were not always adequate, i.e. at levels above the currently requested values for commercial vaccines (post-vaccination seroprotection rate ≧1:40, increases in geometric mean titres ≧2, positive responses ≧30% compared with pre-vaccination), probably because of old age (mean age ≧81 years) and the presence of underlying diseases in a high percentage of volunteers (≧86%). The most frequent chronic diseases found werecardiovascular diseases (48%), endocrine disorders (19%), functional disability (10%) and pulmonary diseases (4%). The post-vaccination values observed in the sequential years were in general similar for A/H3N2 and A/H1N1 vaccine strains. A decrease, however, for some parameters at statistically significant levels, was observed against B antigen following repeated vaccine administrations. Conclusion: Our data seem to support the possibility of a slight impairment of HI antibody response against unaltered influenza vaccine antigens, especially for influenza strains that have circulated for prolonged periods of time. Indeed a tendency to a lower response was found only against B/Beijing antigen, introduced in the vaccine composition in the winter 1995/96, but not against the A/H3N2 and A/H1N1 vaccine strains, which weremore frequently changed.

An influenza B outbreak during the 2007/2008 winter among appropriately immunized elderly people living in a nursing home.

The study evaluated the immunogenicity and efficacy of a trivalent subunit MF59-adjuvanted influenza vaccine (A/Wisconsin/67/05 (H3N2), A/Solomon Islands/3/06 (H1N1) and B/Malaysia/2506/04) in preventing serologically diagnosed infections in a group of 67 institutionalized elderly volunteers during 2007/2008 winter, characterized by co-circulation of drifted A/H3N2, A/H1N1 and B influenza viruses. Influenza vaccination induced a significant increase in the amounts of hemagglutination inhibiting antibodies, both against the vaccine and the epidemic drifted strains. However, vaccination did not prevent the circulation of the new drifted influenza B virus (B/Florida/4/06-like), belonging to the B/Yamagata/16/88-lineage, antigenically and genetically distinct from B/Victoria/2/87-lineage viruses from which the vaccine B strain was derived.

Influenza viruses and cross-reactivity in healthy adults: Humoral and cellular immunity induced by seasonal 2007/2008 influenza vaccination against vaccine antigens and 2009 A(H1N1) pandemic influenza virus

We analyzed humoral and cellular immune responses against vaccine antigens and the new A(H1N1) virus in healthy adults before and after immunization with the 2007/2008 commercially available trivalent subunit MF59-adjuvanted influenza vaccine during the Fall 2007, prior to the emergence of the new virus. Antibody titers were significantly boosted only against the three vaccine antigens. Seasonal vaccination boosted pre-existing cellular responses upon stimulation of peripheral blood mononuclear cells not only with the homologous three vaccine antigens, but also with the heterologous new 2009 A(H1N1) and with a highly conserved peptide present in the stalk region of hemagglutinin (HA). These results show that cross-reactive cell responses against the new virus were present before the circulation of the virus and were boosted by seasonal vaccination. The cross-reactivity of cellular responses might, at least in part, explain the low pathogenicity of the new pandemic virus. The finding of cellular immunity, that can be increased by seasonal vaccination, against the conserved HA peptide, underline the potential use, in human vaccines, of conserved peptides of the stalk region of HA characterized by broad immunogenicity in experimental systems.

Immune response to trivalent inactivated influenza vaccine in young and elderly subjects.

The antibody response (determined using the single radial haemolysis in gel technique) to inactivated whole-virion trivalent influenza vaccine [A/Leningrad/360/86(H3N2), A/Taiwan/5/87 and B/Ann Arbor/1/86], recommended for the 1987-88 winter season in Italy, in 49 elderly (age greater than or equal to 60 years) subjects was compared with the response in 23 young adult (age less than 60 years) volunteers. The subjects were prevalently healthy and a high percentage of young and old people had been repeatedly immunized against influenza in previous years. No significant differences were detected among age groups; moreover, the immune response measured by seroconversion or by a significant rise in antibody titre was constantly low.

Antibody Response to 1995–1996 Influenza Vaccine in Institutionalized and Non-Institutionalized Elderly Women

Background: Concern about poor responsiveness to influenza vaccination by institutionalized elderly people. Objective: To determine whether institutionalized elderly volunteers develop a significant antibody response following influenza vaccine and to compare this response with that of non-institutionalized subjects. Methods: The haemagglutination-inhibiting antibody response after 1995–1996 influenza vaccination [A/Shangdong/9/93 (H3N2), A/Taiwan/1/86 (H1N1), B/Panama/45/90] was estimated in 80 elderly women living in a nursing home and compared with that of 51 non-institutionalized women. Results: No differences were found in the prevaccination status, and, after vaccination, a significant humoral response was elicited both in institutionalized and non-institutionalized elderly subjects against all three influenza strains tested. The immune response of institutionalized patients was satisfactory and significantly higher than that observed in non-institutionalized women. These results were confirmed both by a separate analysis of homogeneous subgroups stratified according to the presence in the two cohorts of potential causes of differential antibody response (prevaccination antibody titre, age, long-term drug treatment, risk factors for influenza infection, and physical disability) and by logistic regression analysis in order to adjust immune responses for the different variables. Conclusion: Influenza vaccination is effective in elderly people living in nursing homes. However, the postvaccination antibody response to influenza vaccine is influenced by different factors directly or indirectly related to residence.

Inhibition of hybrid resistance to lymphomas by inactivated tumor cells in lethally irradiated mice.

Two murine lymphomas, L5MF-22 of B10.129(5M) (H-2b) origin and P388 of DBA/2 (H-2d) origin, were inoculated into lethally irradiated hybrid (C57BL/6 x DBA/2)F1 (B6D2F1) mice (H-2b/H-2d). Marked localized graft resistance was found in the spleen and occasionally in the liver of recipient mice as a result of a non-T-dependent hybrid resistance (HR). Significant reduction of HR of B6D2F1 mice could be obtained when viable lymphoma cells were inoculated along with inactivated cells of the same tumor or of genetically related leukemias. These results suggest that in vivo competition for HR effectors can take place in mouse spleen and liver leading to a depression of the localized resistance.