Recombinant Virus Vaccines

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

(1)In 2022 mpox, caused by monkeypox virus (MPXV), spread worldwide, causing nearly 100,000 mpox cases in over 100 countries. The modified vaccinia Ankara (MVA) vaccine Jynneos reduced disease in at-risk populations but failed to deliver complete protection. In 2025, we continued our studies of an mRNA-lipid nanoparticle vaccine expressing four MPXV surface proteins developed by Moderna and further demonstrated that single inoculation protects mice against intranasal infection and that two vaccinations provided protection for at least 4 months. Bioluminescence imaging showed that vaccination greatly reduced or prevented virus replication and spread from intranasal, rectal, and dermal inoculation sites. Furthermore, immunocompetent and immunodeficient mice lacking mature B and T cells that received serum from mRNA-immunized macaques before or after VACV challenge were protected. (2) In another study, immunization of non-human primates with the mRNA conferred protection against a lethal MPXV challenge and provided better viral control and disease attenuation compared with MVA, highlighting the potential for mRNA vaccines to mitigate future pandemic threats.(3) Virus-like particle (VLP) vaccines have been shown to provide higher and more lasting immune responses than soluble proteins. We constructed VLP mpox vaccines in which three modified proteins from MPXV clade Ia were conjugated individually or together to a scaffold that accommodates up to 60 ligands using the SpyTag/SpyCatcher nanoparticle system. Immunization of mice with VLPs induced higher anti-MPXV virus neutralizing antibodies than their soluble protein counterparts or MVA. Additionally, the VLP vaccine reduced the replication and spread of the virus at intranasal and intrarectal sites of inoculation. VLPs induced higher neutralizing activity than the Jynneos MVA vaccine in rhesus macaques, and the VLP-induced antiserum provided better protection against virus infection than the Jynneos-induced antiserum when passively transferred to mice. (4) In another study, we compared the immunogenicity and protective efficacy of the JYNNEOS MVA vaccine, replication competent ACAM2000 vaccine and a subunit adenovirus vaccines in rhesus macaques. ACAM2000 provided near complete protection to a high dose MPXV challenge, whereas JYNNEOS and subunit vaccines provided incomplete protection. Only ACAM2000 produced substantial MPXV neutralizing antibody consistent with its better protection. (5) In adults that received 1 or 2 doses of MVA vaccine, binding antibodies to MPXV antigens peaked at 3 weeks but declined to low levels by 12 months and MPXV neutralizing antibodies were minimal at both times. These results suggest that Jynneos vaccine boosting may be beneficial.