Enhanced Immune Responses to HIV-1 Envelope Elicited by a Vaccine Regimen Consisting of Priming with Newcastle Disease Virus Expressing HIV gp160 and Boosting with gp120 and SOSIP gp140 Proteins

Abstract

dNewcastle disease virus (NDV) expressing HIV-1 BaL gp160 was evaluated either alone or with monomeric BaL gp120 and BaL SOSIP gp140 protein in a prime-boost combination in guinea pigs to enhance envelope (Env)-specific humoral and mucosal immune responses. We showed that a regimen consisting of an NDV prime followed by a protein boost elicited stronger serum and mucosal Th-1-biased IgG responses and neutralizing antibody responses than NDV-only immunizations. Additionally, these responses were higher after the gp120 than after the SOSIP gp140 protein boost. It is believed that an effective vaccine against HIV-1 should induce potent systemic and mucosal immune responses. Therefore, the use of live-virus vectored vaccines capable of replicating at mucosal surface has become very attractive. To induce robust antibody (Ab) responses, several of these vectored vaccines are being evaluated either alone or in several prime-boost combinations using different forms of HIV envelope (Env) protein (1-4). It has been reported that a viral vector prime and protein boost regiment could elicit protective immunity to HIV-1 in nonhuman primates (4-7) and, recently, in humans in an RV-144 vaccine trial (8). Among the different viral vector systems under evaluation for HIV, Newcastle disease virus (NDV), an avian paramyxovirus, has the characteristics desired for an HIV-1 vaccine. There is no preexisting immunity to NDV in humans. NDV infects via the intranasal and oral routes and induces both mucosal and systemic immune responses (9-17). Previously, we demonstrated the potential of NDV as a vaccine vector for HIV-1 (14-17). However, the concept of an NDV vector prime followed by Env protein boost to increase immune responses to HIV has never been evaluated previously.In order to identify an improved vaccination regimen that elicits a higher level of anti-HIV humoral as well as mucosal immune responses, an avirulent recombinant NDV (rNDV) strain, LaSota, expressing gp160 of HIV-1 strain BaL.1 was used as a prime followed by a boost with purified monomeric gp120 and trimeric SOSIP gp140 proteins in this study. The construction and characterization of rNDV expressing gp160 (rNDV-gp160) were described before (16). Briefly, the gp160 protein expressed by rNDV was detected on infected cell surfaces and was also incorporated into the NDV virion. Further, gp160 present in infected cells and in the virion formed oligomers which were recognized by conformationally dependent monoclonal Abs (MAbs). The BaL gp120 and SOSIP gp140 proteins (18) were produced as described previously (19). The BaL SOSIP gp140 protein has been characterized by Dey et al. (19), and they demonstrated that BaL SOSIP gp140, expressed in HEK 293 cells, was a mixture of monomers, dimers, and trimers. Guinea pigs were used to evaluate the humoral and mucosal immune responses induced by this vaccine regimen. Female Hartley guinea pigs obtained from Charles River Laboratories were assigned to four groups (n ϭ 3/group) as shown in Fig. 1. Each animal in all the groups recei...

Newcastle Disease Virus-Based Vectored Vaccine against Poliomyelitis

“…Booster immunization was performed 3 weeks after the first immunization, and both blood serum and vaginal wash samples were collected before immunization and at weeks 3, 4, 5, 7, 9, and 11 postimmunization. The animals did not show any adverse effects associated with immunization, as was observed previously even for multiple cycles of administration of NDV-based vaccines (40). Replication of NDV was confirmed in all animals, as evidenced by the development of a serum anti-NDV IgG response.…”

Engineering of Live Chimeric Vaccines against Human Metapneumovirus

“…An exogene can be placed at the gene junction between any two genes of the virus, yet the 3 rd position has been found to be the most optimal for NDV vector [149,182,185,186] with the 1 st and the 2 nd ones being the least optimal [148,149]. NDV has been used for vectoring the antigens of RSV [185], AMPV [187][188][189], HIV [149,190,191], HPIV3 [182], influenza A virus [192], SARS-coronavirus [186], Nipah virus [193], and Ebola virus [194]. Examples of NDV vectoring pneumoviral antigens are reported in Table 4.…”

Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines

“…The HIV Gag and Env proteins have been expressed by NDV vector [ 14 , 28 , 29 , 30 ]. The expression level of Gag protein was optimized using different insertion sites in the NDV genome.…”

“…These results suggest that vaccination with a single NDV vector coexpressing Env and Gag represents a promising strategy to enhance immunogenicity and protective efficacy against HIV. In addition, heterologous prime (NDV expressing gp160) and boosting (purified gp120 protein) approach induced high neutralizing antibody titer in guinea pigs [ 30 ]. These findings suggest that vaccination with multiple HIV antigens in combination can broaden antiviral immune responses.…”