Coadministration of Cidofovir and Smallpox Vaccine Reduced Vaccination Side Effects but Interfered with Vaccine-Elicited Immune Responses and Immunity to Monkeypox

Abstract

While the smallpox vaccine, Dryvax or Dryvax-derived ACAM2000, holds potential for public immunization against the spread of smallpox by bioterror, there is serious concern about Dryvax-mediated side effects. Here, we report that a single-dose vaccination regimen comprised of Dryvax and an antiviral agent, cidofovir, could reduce vaccinia viral loads after vaccination and significantly control Dryvax vaccination side effects. However, coadministration of cidofovir and Dryvax also reduced vaccine-elicited immune responses of antibody and T effector cells despite the fact that the reduced priming could be boosted as a recall response after monkeypox virus challenge. Evaluations of four different aspects of vaccine efficacy showed that coadministration of cidofovir and Dryvax compromised the Dryvax-induced immunity against monkeypox, although the covaccinated monkeys exhibited measurable protection against monkeypox compared to that of naïve controls. Thus, the single-dose coadministration of cidofovir and Dryvax effectively controlled vaccination side effects but significantly compromised vaccine-elicited immune responses and vaccine-induced immunity to monkeypox.

Co-administration of the broad-spectrum antiviral, brincidofovir (CMX001), with smallpox vaccine does not compromise vaccine protection in mice challenged with ectromelia virus

“…Representative experiment of N = 3 with 12-15 mice/group. of protective immunity against subsequent OPV challenge (Grosenbach et al, 2008;Israely et al, 2012;Silvera et al, 2009) although this observation was not universal since there is one report in which a combined CDV and vaccine regimen did not result in protective immunity (Wei et al, 2009). In the studies described in this report, we evaluated the efficacy of Dryvax and ACAM2000 smallpox vaccines when administered with a BCV regimen.…”

Expansion, Reexpansion, and Recall-Like Expansion of Vγ2Vδ2 T Cells in Smallpox Vaccination and Monkeypox Virus Infection

“…3, middle). Few V␥2 T cells were detected in the lung tissues from three other vaccinia virus/cidofovir-vaccinated macaques in which no or only subtle gross/histology changes in tissues were seen at necropsy (23). Surprisingly, despite the fact that a majority of naïve control macaques did not show major expansion of V␥2V␦2 T cells in the blood during fatal MPV infection, V␥2 T cells were apparently detectable in their inflamed lung tissues at the time they developed fatal monkeypox (Fig.…”

“…These animals received routine serum and viral/microbiological tests in three nonhuman primate facilities. Vaccination and MPV challenge were done as previously described (23). After the viral infections, complete blood count and differential data did not support active superimposed bacterial infections.…”

“…The copies of vaccinia virus or MPV A33R genes in PMBC were measured by real-time quantitative PCR (23).…”

“…Peripheral blood mononuclear cells (PBMC) were used to measure gamma interferon-positive (IFN-␥ ϩ ) V␥2V␦2 T cells in response to HMBPP stimulation (40 g/ml) (14). Enzyme-linked immunospot (ELISPOT) assays for virus-specific ␣␤ T-cell responses were done using pooled 15-mer peptides overlapping by 11-mer and spanning the entire H3L protein (23).…”