Vaccinia-based COVID-19 vaccines confer immunity in hamster model

The currently deployed SARS-CoV-2 vaccines are mRNA or adenovirus-based and have proven effective in reducing the probability of infection and severity of disease upon infection. These vaccines, however, require a carefully controlled cold chain, making large-scale manufacturing and delivery difficult and costly.

The vaccinia virus is an enveloped virus that is closely related to the virus that causes smallpox, and has therefore been used as a live-virus vaccine against the illness. It can be lyophilized, and therefore is less dependent on an intact cold chain than mRNA-based vaccines. Poxviruses, like vaccinia, are unique among DNA viruses as they replicate in the cytoplasm of the host cell rather than the nucleus. Recombinant vaccines have also been produced using a vaccinia vector, wherein foreign genes can be expressed within a host and subsequently induce an immune response.

Study: Vaccinia virus-based vaccines confer protective immunity against SARS-CoV-2 virus in Syrian hamsters. Image Credit: Numstocker / Shutterstock

In a paper recently uploaded to the preprint server bioRxiv* by Kulkarni et al. (August 3, 2021), the potential of vaccinia virus-based vaccines expressing the full-length SARS-CoV-2 spike protein is examined in mice and Syrian hamsters. The findings report that the vaccine generates high titers of neutralizing antibodies with good activity towards SARS-CoV-2 variants of concern.

Two strains of vaccinia were utilized for comparison by the group: modified vaccinia Ankara (MVK) and New York City Board of Health viral strain of smallpox vaccine (v-NY), the first of which is a growth-restricted vector that has been demonstrated to be safe and effective against other viral diseases such as HIV, SARS-CoV, and MERS-CoV, while the latter is replication-competent but with reduced virulence compared to the standard Dryvax smallpox vaccine.

How was the study performed?

The full-length SARS-CoV-2 spike protein sourced from the wildtype Wuhan strain was made to express on the surface of each vaccine vector. The prepared vaccines were administered to mice under three differing regimens: large MVA dose followed by a smaller second dose, small v-NY dose followed by small MVA boost, and large v-NY dose followed by small MVA dose. Sera was collected from the animals 2 weeks following the first and second doses of the vaccines, respectively, and in some cases, the spleen was harvested for further examination.

At each time point and under each administration regimen, the mice developed higher titers of neutralizing antibodies towards SARS-CoV-2 than the control group, in particular among those receiving the v-NY vaccine initially. Secretion of cytokines TNF-α and IFN-was noted to be higher amongst vaccinated mice than IL-4 and IL-6, indicating that a Th1-based immune response had been instigated and T cells activated, inducing non-inflammatory protection. CD8+ T effector memory cells were also noted to be elevated in the spleens of those mice sacrificed, while the levels of CD4+ cells were not altered, supporting this observation.

Sera collected almost 5 months following the vaccine regimen still bore around 70% of the spike-specific antibodies seen at the two-week post-vaccination time point, demonstrating that the vaccines elicit a long-lasting immune response towards SARS-CoV-2.

Syrian hamsters are often used in research as a model for respiratory infection in humans. The group subjected the animals to the same dosing regimen as applied to the mice, finding that similarly high neutralizing antibody titers were obtained as in mice under each course. Given the more comparable lungs of Syrian hamsters to humans, the viral load within the lungs was assessed, finding that those in the control group bore extremely high titers, indicating infection, while in those receiving any combination of the vaccine, no viral particles were detected.

The v-NY vaccine was noted to generate a greater immune response than the MVA vaccine overall, reaching protective levels even after only a single dose, with antibody titers not then rising notably upon administration of the second dose. Interestingly, however, the sera of animals given the heterogeneous regimen bore higher antibody titers and exhibited improved cross-reactivity towards SARS-CoV-2 variants of concern over those given a homogenous dose.

As the v-NY vaccine can be dried and delivered without the need of careful cold chain monitoring, it may provide an ideal solution to the global demand for vaccines, and this paper suggests that it is capable of imparting relevant levels of immunity after only a single dose. Introducing heterogeneity between the first and second doses of the vaccine has also been suggested by other studies to improve the spectrum of SARS-CoV-2 lineages that are effectively neutralized. If this proves to be the case, then initial and urgent first vaccine doses could be provided by the storage stable v-NY vaccine, with subsequent and less time-sensitive doses originating from any other source.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Michael Greenwood

Michael graduated from Manchester Metropolitan University with a B.Sc. in Chemistry in 2014, where he majored in organic, inorganic, physical and analytical chemistry. He is currently completing a Ph.D. on the design and production of gold nanoparticles able to act as multimodal anticancer agents, being both drug delivery platforms and radiation dose enhancers.