Safety profile of recombinant canarypox HIV vaccines

CD40L expressed from the canarypox vector, ALVAC, can boost immunogenicity of HIV-1 canarypox vaccine in mice and enhance the in vitro expansion of viral specific CD8+ T cell memory responses from HIV-1-infected and HIV-1-uninfected individuals

“…The CD4 + T-cell-replacement activity of CD40L in our DC co-culture experiments is especially intriguing in the setting of development of a therapeutic vaccine for HIV-1. One advantage of canarypox vector is its high-profiled safety, which has been demonstrated in both animal studies and clinical trials [5,9,29,48]. Another advantage of canarypox vector is that as a DNA virus that can only abortively infect mammalian cells, the target gene will be expressed transiently, which may be especially important for the expression of costimulatory molecules, such as CD40L, since long-term presence of costimulatory molecules might lead to autoimmunity or immunosuppression [49][50][51].…”

“…ALVAC HIV-1 vaccine is a candidate HIV-1 vaccine, which is now in Phase III clinical trials [7,8] (http://www.iavireport.org/specials/OngoingTrialsofPreventiveHIVVaccines.pdf). Previous studies have shown that ALVAC HIV-1 vaccines are safe [9], and unlike adenovirus vectors, may not be limited by pre-existing anti-vector immunity [10,11]. However, ALVAC immunogenicity in humans is low, eliciting HIV-1-specific cytotoxic CD8 + T cell (CTL) responses in less than 25% of normal volunteers in clinical studies [12][13][14], implying that further efforts need to be done to improve the immunogenicity of current canarypox HIV-1 vaccines.…”

Sex differences in injection site reactions with human vaccines

“…This explanation may also be applicable to infants and children as although ultrasound studies [119][120][121][122][123] have shown no sex difference in subcutaneous layer thickness, in the MRI/CT study by Lippert and Wall, 24 females had thicker subcutaneous layers than males, thigh (subjects 2 months to 6 years) and deltoid (12 months to 18 years). These authors contend that the discrepancy between ultrasound and MRI/CT scan generated data reflects greater accuracy of the latter in measuring and showing the distinction between muscle and fat layers and lack of compression of the site being screened with MRI/ CT scanning compared with ultrasonography.…”

“…They suggested that because women would be likely to have smaller deltoid muscles than men, injection into this muscle would cause more muscle distention and hence give an increased rate of pain 24 284 M, 132 F, mean age 35 ± 9.6 yrs. ALVAC plus subunit, n = 710; 443 M, 267 F, mean age 34 ± 9.6 yrs.…”

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“…But the disadvantage lies that with repeated use, host-induced antibodies can neutralize the vector thereby limiting its efficacy. 28,29 Development of vector-based viral vaccine named as Vaccinia 30 (Poxvirus) long 20 years ago further extended with the modified Vaccinia virus Ankara (MVA), 31 avian poxviruses (fowl pox, 32 canary pox 33,34 ). The probability of combination of viral vector-based vaccine with other vaccines modalities gives an added benefit.…”