Enhanced CD8+ T cell response to HIV-1 env by combined immunization with influenza and vaccinia virus recombinants

There is an urgent need for human immunodeficiency virus (HIV) vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions, although the infections were asymptomatic. Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins. SIV-specific CD8 T-cell responses bearing the mucosal homing marker ␤7 integrin were induced by vaccination of naïve animals. Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection. Sequential vaccination with influenza virus-SIV recombinants of different subtypes (H1N1 followed by H3N2 or vice versa) produced only a limited boost in immunity, probably reflecting T-cell immunity to conserved internal proteins of influenza A virus. SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia. Although our results suggest that influenza virus-HIV vaccines hold promise for the induction of mucosal immunity to HIV, broader antigen cover will be needed to limit cytotoxic T-lymphocyte escape.

Section: Discussionsupporting

confidence: 60%

mentioning

confidence: 99%

Evaluation of Recombinant Influenza Virus-Simian Immunodeficiency Virus Vaccines in Macaques

Sexton

Rose

Reece

et al. 2009

“…The induction of strong cytotoxic T-lymphocyte (CTL) responses that are able to control viral replication and prevent clinical disease progression was shown to be a necessary component of successful vaccination in a rhesus macaque model (8, 10, 12, 13, 77, (5,10,14,25,34,40,44,45,64,86,87) and bacterial (3, 29, 37, 46, 47, 55-57, 62, 73, 80, 89, 90) vectors expressing HIV-1 antigens were reported to elicit potent HIV-1-specific CTL responses, including efficient mucosal immunity. The role of CTLs in inducing and maintaining efficient immune responses was addressed in a number of HIV-1 vaccine trials (43).…”

mentioning

confidence: 99%

Magnitude and Frequency of Cytotoxic T-Lymphocyte Responses: Identification of Immunodominant Regions of Human Immunodeficiency Virus Type 1 Subtype C

Novitsky

Cao²,

Rybak

et al. 2002

105

(68), (iv) a high level of viral diversity (24,72,95), (v) preferential CCR5 coreceptor usage (1,19,78,92), and (vi) a number of unique subtype signatures across the viral genome (39,72,82,84).Vaccine protection against pathogenic simian immunodeficiency virus or simian-human immunodeficiency virus was demonstrated in a series of experiments with nonhuman primates (reviewed in references 6, 49, and 65). The induction of strong cytotoxic T-lymphocyte (CTL) responses that are able to control viral replication and prevent clinical disease progression was shown to be a necessary component of successful vaccination in a rhesus macaque model (8, 10, 12, 13, 77, 91;

“…Immunization of mice with irradiated sporozoites elicits CS-specific CD8 ϩ T cells, which mediate the inhibition of development of the parasite's liver stages (29). These antigen-specific CD8 ϩ T cells can also be induced by immunizations with several recombinant viruses, which, by entering the cytoplasms of antigenpresenting cells, induce "foreign" antigen processing and presentation by the class I pathway (18).Priming-boosting immunization approaches using two different vectors expressing the same antigen have demonstrated great potential as vaccination strategies, resulting in the induction of potent immune responses against malaria (5, 15, 25-27, 30, 33) and other infectious diseases, including AIDS (1,16,20,28). A number of earlier experiments pioneered the use of different vectors in priming-boosting regimens of immunization.…”

mentioning

confidence: 99%

“…Priming-boosting immunization approaches using two different vectors expressing the same antigen have demonstrated great potential as vaccination strategies, resulting in the induction of potent immune responses against malaria (5, 15, 25-27, 30, 33) and other infectious diseases, including AIDS (1,16,20,28). A number of earlier experiments pioneered the use of different vectors in priming-boosting regimens of immunization.…”

mentioning

confidence: 99%

Induction of Protective Immunity against Malaria by Priming-Boosting Immunization with Recombinant Cold-Adapted Influenza and Modified Vaccinia Ankara Viruses Expressing a CD8⁺-T-Cell Epitope Derived from the Circumsporozoite Protein ofPlasmodium yoelii

González‐Aseguinolaza¹,

Nakaya

Molano³

et al. 2003

Self Cite

We immunized mice with an attenuated (cold-adapted) influenza virus followed by an attenuated vaccinia virus (modified vaccinia virus Ankara), both expressing a CD8؉ -T-cell epitope derived from malaria sporozoites. This vaccination regimen elicited high levels of protection against malaria. This is the first time that the vaccine efficacy of a recombinant cold-adapted influenza virus vector expressing a foreign antigen has been evaluated.Malaria remains a major cause of morbidity in tropical and subtropical areas of the five continents, with an estimated 350 to 500 million individuals displaying clinical manifestations each year. In addition, the increasing drug resistance of the two most prevalent severe malaria species infecting humans, Plasmodium falciparum and Plasmodium vivax, makes it important to develop effective and long-lasting antimalaria vaccines. The feasibility of a prophylactic malaria vaccine for humans has been demonstrated with volunteers immunized with irradiated sporozoites of P. falciparum and P. vivax. This immunization protocol resulted in complete protection from disease after challenge of vaccinees by the bite of laboratory-bred mosquitoes infected with viable sporozoites (10). This proof of principle, obtained in the late 1970s, was corroborated by various investigators (9, 23).In 1976 we described the circumsporozoite (CS) protein, which covers the entire sporozoite surface with a thick coat (11). Injection, into mice, of minimal amounts of an anti-CS monoclonal antibody directed against the CS repeats of Plasmodium berghei (its major B cell epitope) abolished sporozoite infectivity (32). The CS protein is expressed not only by sporozoites but also by parasite-infected hepatocytes. Immunization of mice with irradiated sporozoites elicits CS-specific CD8 ϩ T cells, which mediate the inhibition of development of the parasite's liver stages (29). These antigen-specific CD8 ϩ T cells can also be induced by immunizations with several recombinant viruses, which, by entering the cytoplasms of antigenpresenting cells, induce "foreign" antigen processing and presentation by the class I pathway (18).Priming-boosting immunization approaches using two different vectors expressing the same antigen have demonstrated great potential as vaccination strategies, resulting in the induction of potent immune responses against malaria (5, 15, 25-27, 30, 33) and other infectious diseases, including AIDS (1,16,20,28). A number of earlier experiments pioneered the use of different vectors in priming-boosting regimens of immunization. Specifically, mice were primed with a recombinant influenza virus and given boosters with a recombinant vaccinia virus; both viruses expressed sequences of the CS protein of Plasmodium yoelii (18). This regimen of immunization elicited a high degree of protection against sporozoite challenge. It was also shown that immunizing mice with both recombinant influenza and vaccinia viruses, which express the B-cell and cytotoxic CD8ϩ -T-cell epitopes of P. falciparum, resulted in CSsp...