NEWS

Human Vaccines & Immunotherapeutics 8:10, 1366-1369; October 2012; © 2012 Landes Bioscience

Human Vaccines: News

Chickenpox cases in the US drop by 80%
The Centers for Disease Control and Prevention According to a recent CDC report1 national vaccination increases, the CDC expects to see
(CDC) reported a drop in varicella incidence surveillance has continuously improved since further declines in chickenpox.
(chickenpox) of almost 80% between 2000 1996. The number of states with adequate While most cases are mild, lasting five to
and 2010. chickenpox reporting systems jumped from ten days, some people become seriously ill.
A single dose of varicella vaccine was first 12 to 31 between 2000 and 2010. In these Symptoms of this common infectious disease
recommended for use in the US in 1996. Since 31 states, chickenpox dropped from 43 cases include an itchy blister-like rash, tiredness,
2006, a second routine dose has been recom- per 100,000 population in 2000 to nine cases headache and fever. Adults typically become
mended. Children get the first dose between per 100,000 in 2010 (79%). The report also sicker than children.
12 and 15 months of age, and the second shows that in the four years after the two-dose
dose between 4 and 6 years of age, or at least vaccine was introduced for children in 2006, Reference
three months after the first dose. Teenagers cases of chickenpox declined about 70%, with 1. http://www.cdc.gov/mmwr/preview/mmwrhtml/
and adults who have not had chickenpox or the the greatest declines being observed among mm6132a2.htm?s_cid=mm6132a2_w
chickenpox vaccine are recommended to also children aged 5 to 9 years of age. As two-dose
get two vaccine doses at least four weeks apart.

Novel immunotherapy for breast, ovarian and prostate cancer successfully

completes Phase 1
Recently, the Canadian clinical stage vaccine cancer, 7 ovarian cancer, 13 prostate can- vaccination suggesting favorable immune
company Immunovaccine Inc. published posi- cer) in five centers in the US. Patients were induction potential for DPX-0907, and 64%
tive results from a Phase 1 clinical trial of its divided into two dose/volume cohorts (0.25 maintained a persistent response at one
DPX-0907 cancer vaccine in the Journal of or 1mL doses) and received three injections month following the third dose.
Translational Medicine.1 The published paper of the active immunotherapy three weeks While the focus of the study was on eval-
details new findings on specific polyfunctional apart. Safety was assessed in eleven patients uating antigen-specific CD8+ T-cells, CD4
T-cell responses generated by DPX-0907, as in the low-dose group and eleven in the high- responses against a T-helper peptide included
well as previously announced positive safety dose group, after one of the ovarian cancer in the vaccine were also detected. The CD4
and immune response findings from the study. patients in the high-dose group discontinued responses correlated with antigen-specific
DPX-0907 is a unique multi-targeted thera- the study, leaving a total of 22 patients with CD8+ T cell responses in the same assay, sup-
peutic vaccine designed to train the immune eleven patients in each of the dosage groups. porting the hypothesis that the CD4 responses
system, in particular T-cells, to recognize and Immunogenicity results are based on an may have facilitated the generation of the
destroy cancer cells. The vaccine combines analyis of nine evaluable patients in the low- specific CD8+ T cells observed.
seven tumor-associated antigens (TAAs) – all dose group and nine evaluable patients in the “We believe that the breadth of positive
of them naturally processed HLA-A2 restricted high-dose group. DPX-0907 was generally well data generated by this very first clinical study
peptides presented by breast, ovarian and tolerated and considered safe at both dose of DPX-0907 and the DepoVax technology
prostate cancer cells - with Immunovaccine’s levels. Furthermore, the study demonstrated provides support for the potential therapeutic
novel DepoVax adjuvanting delivery platform. antigen-specific CD8+ T-cell responses follow- value of both the product and the platform.
DepoVax creates a depot effect upon vaccina- ing vaccination. Of the trial’s evaluable cancer Importantly, the valuable information that we
tion, resulting in prolonged presentation of patients, 61 % (11/18) showed the desired have learned from this study, in terms of safety,
antigens and adjuvant to the immune system. targeted T-cell responses against one or more immune response and patient profile, provides
Incorporating multiple target antigens allows of the seven TAAs contained in the vaccine. Immunovaccine with critical insight into how
the vaccine to attack cancer cells through This number was even higher (89 %, or 8/9) best to proceed with the clinical development
multiple avenues and potentially reduces the when looking only at patients with breast or of this novel approach to cancer immunother-
chance for cancer cells to escape the therapy. ovarian cancer. Immune monitoring also dem- apy,” said Dr. Marc Mansour, Immunovaccine’s
The open-label, dose-escalation Phase 1 onstrated the generation of antigen-specific chief scientific officer.
study, designed to examine the safety and T-cell memory with the ability to secrete mul-
immune activating potential of DPX-0907 in tiple Type 1 cytokines. Reference
advanced stage breast, ovarian and prostate Of the study’s immune responders, 73% 1. Berinstein NL, et al. J Transl Med. 2012 Aug
cancer patients, included 23 subjects (3 breast generated a response following the first 3;10(1):156.

1366 Human Vaccines & Immunotherapeutics Volume 8 Issue 10

 NEWS News, Policy and Profiles

Important progress for Inovio’s universal influenza vaccine

Inovio Pharmaceuticals recently announced H1N1 strain that caused the 1918 Spanish did not generate vaccine-induced response
positive interim data from a Phase 1 trial of its flu. These unmatched influenza strains were rates against the unmatched strains.
SynCon universal H1N1 influenza vaccine. The used to assess the generation of HAI titers The achievement of protective titers
vaccine generated protective hemagglutina- meeting or exceeding 1:40. HAI titer of 1:20 against multiple unmatched strains represents
tion inhibition (HAI) titers against some of the is regarded as a positive vaccine response, a major step towards Inovio’s ultimate goal
most prevalent strains of the past 100 years. while 1:40 is considered a protective immune to develop a universal influenza vaccine to
Inovios‘ SynCon vaccines are designed response against influenza. The interim data protect against known and newly emerging
to provide universal cross-strain protection analysis showed that a significant percentage strains of influenza.
against known as well as newly emergent of subjects immunized with Inovio’s SynCon “With respect to influenza, our ultimate
unmatched strains of pathogens such as influ- vaccine had a HAI titer ≥1:40 against each of objective is to develop a universal vaccine
enza. The two synthetic H1N1 hemagglutinin the nine H1N1 strains tested, demonstrating capable of providing years of true preemptive
(HA) plasmids, tested in the current Phase 1 the vaccine’s broad cross-reactive coverage. protection across subtypes and strains,” said
study, incorporate sequence information from A control group was immunized with the sea- Dr. J. Joseph Kim, Inovio’s President and CEO.
multiple divergent strains. The vaccines are sonal TIV (trivalent influenza vaccine) matched “This is a challenging goal, but this proof-
not matched to any of the historical flu strains. to the current H1N1 seasonal flu strain (A/ of-principle H1N1 data demonstrates the
Healthy adults received these plasmids up California/07/09). Compared to the control potential of our SynCon approach to generate
to three times via intradermal electroporation, group, subjects immunized with Inovio’s vac- cross-protective HAI titers against multiple
and the vaccine was well tolerated. Blood cine generated a higher or similar percentage unmatched influenza strains. These results
samples of vaccinated subjects were exposed of positive HAI titer responders against all of are an important addition to our previously
to each of the nine key H1N1 viruses in cir- the strains except for A/California/07/09. As reported H5N1 phase I data and a validating
culation over the last 100 years: eight were anticipated, the TIV recipients generated the achievement on our ongoing effort to develop
H1N1 strains used to formulate the seasonal best HAI titers against the matched strain, but a safe vaccine that provides immunity against
vaccines of the last 25 years; one was the the ever-changing influenza virus.”

Vaccine against ricin exposure successful in phase 1B

The development stage biopharmaceutical Medical Center (UTSW), aimed to evaluate the first vaccination, with 60% remaining positive
company Soligenix recently announced posi- long-term safety and immunogenicity of esca- at one year.
tive results from a phase 1B clinical trial of lating doses of RiVax up to one year after Results of the Phase 1b study have recently
an aluminum hydroxide (Alum) adjuvanted primary vaccination. The vaccine was admin- been published in the journal Clinical and
formulation of RiVax, a vaccine designed to istered by intramuscular injection to healthy Vaccine Immunology.1 Results of the prior Phase
protect against Ricin toxin exposure. volunteers at 0, 6 weeks, and 6 months in doses 1a trial of RiVax were published in the journal
Ricin toxin, classified by the CDC as a of 10 and 100µg. RiVax was well tolerated in Proceedings of the National Academy of Science
Category B biological agent, is a protein con- all individuals with only mild side effects. At of the USA.2
sisting of A and B subunits that can be extracted the peak of antibody titers two weeks after the “These positive results indicate a route
from the beans of the castor plant, Ricinus com- third vaccination, all of the subjects had devel- forward for the further development of the
munis. Once one is exposed to lethal doses of oped neutralizing antibodies against ricin toxin. vaccine in larger and more definitive trials in
ricin, death is irreversible after four hours and When comparing peak antibody titers obtained humans and to provide the additional corre-
takes three to five days to kill an individual. in the Phase 1b trial to that of the prior Phase lates of protective immunity in pivotal animal
Currently there are no FDA approved thera- 1a trial which used an Alum-free formulation studies,” said Dr. Robert N. Brey, Chief Scientific
peutics of vaccines that can protect against of RiVax, all subjects in the low dose group (10 Officer of Soligenix. “The Phase 1b results dem-
ricin toxin exposure or reverse its effects once µg) of the Phase 1b trial developed neutralizing onstrate that well-characterized adjuvants can
exposed. antibodies with the Alum formulation of RiVax improve the performance of highly purified
Soligenix is a world leader with RiVax in compared to only one of five subjects in the subunit antigens such as the one contained in
the field of ricin toxin vaccine research. The low dose group of the Alum-free vaccine. In RiVax. The next steps for the development of
recombinant subunit vaccine, developed to the high dose group (100 µg), peak neutral- RiVax will include the evaluation of secondary
protect against exposure to ricin toxin, contains izing titers were four-fold higher with the Alum adjuvants to enhance the induction of neutral-
a genetically altered version of ricin A chain formulation as compared to the Alum-free for- izing antibodies in fewer doses and the employ-
with two mutations that inactivate the inherent mulation, with total antibody anti-Ricin titers ment of our ThermoVax technology to stabilize
toxicity of the ricin molecule. 17-fold higher. All vaccinees in the Phase 1b the ingredients of the vaccine for long-term
The Phase 1b trial, conducted by investiga- trial were seropositive at nine months after the storage at ambient temperature conditions.”
tors at the University of Texas Southwestern

www.landesbioscience.com Human Vaccines & Immunotherapeutics 1367

 References
1. Vitetta ES, et al. Clin Vaccine Immunol 2012;
19:1697-9.
2. Vitetta ES, et al. Proc Natl Acad Sci U S A
2006;103:2268-73.

BCG could help reverse Type 1 Diabetes

According to a new study, the tuberculosis Subjects were followed for 20 weeks. Two of is not an attractive commercial opportunity
vaccine bacillus Calmette-Guérin (BCG), which the three vaccinated patients had signs of with an inexpensive generic vaccine such as
has been in use for 90 years, may help reverse renewed insulin production. Specifically, BCG BCG. The researchers are trying to raise the
Type 1 diabetes (T1D) and reduce the life-long stimulates innate immunity by inducing the money to pay for larger clinical trials. So far, the
need for insulin injections. host to produce tumor necrosis factor (TNF), Faustman lab has received from private donors
About three million Americans suffer from which, in turn kills pathogenic T cells and $11M of the $25M needed to pay for the next
T1D, a condition usually diagnosed in child- restores pancreatic β-cell function through stage of testing.
hood. In order to control their levels of blood regeneration. BCG , a weakened form of the tubercu-
sugar, T1D patients must inject insulin daily. “These patients have been told their pan- losis bacteria, is approved by the FDA as an
Their bodies do not produce the hormone creases were dead,” said study lead author Dr. injectable vaccine for tuberculosis, but is not
as a result of an errant immune system that Denise Faustman, director of Harvard-affiliated generally recommended for use in the US. The
destroys insulin-producing β-cells in the pan- Massachusetts General Hospital’s immunobi- vaccine also is approved for intravesical use
creas. No targeted immunotherapies yet exist ology laboratory. “We can take those people, for bladder cancer. In Italy, the vaccine‘s ability
to reverse T1D in humans despite some prom- give them a very low dose twice, and see their to raise levels of cell-killing TNF is being stud-
ising clinical data. However, in a rodent model pancreases kick in and start to make small ied as a way to treat multiple sclerosis (MS).
of T1D, BCG was shown to reverse disease by amounts of insulin.“ Researchers found that the vaccine may pre-
restoring insulin secretion. Dr. Faustman and her colleagues at vent progression of brain lesions in patients
The result seen in animals has been con- Massachusetts General in Boston are working with advanced stages of MS.
firmed in a small human study, published to continue clinical testing of the vaccine. But
in the journal PLoS One.1 Researchers from there is no interest from major pharmaceu- Reference
Harvard University administered two doses of tical companies in developing the vaccine 1. Faustman DL, et al. PLoS One. 2012;7(8):e41756
BCG to three adults with long-term T1D, with as a possible cure for T1D, according to Dr.
three T1D patients serving as placebo controls. Faustman. One obvious reason is that there

HPV vaccine: effective, when given early

The human papilloma virus (HPV) vaccine (409 women; 59% vaccinated). Participants HPV in vaccinated participants should be inter-
can decrease prevalence of vaccine-type HPV were tested for cervicovaginal HPV DNA and preted with caution but warrants further study.
strains in vaccinated women, and there is completed a questionnaire. Propensity score Another recent study found that more than
evidence of heard protection in unvaccinated weighting was used to balance differences in half of girls 13 years and older already have an
individuals. To be most effective it is important covariates between the 2 surveillance studies. HPV infection. The study, recently published in
that the vaccine is given before girls and boys The researchers found that among all par- the journal Archives of Pediatric and Adolescent
become sexually active. ticipants (mean age, 19 years), the prevalence Medicine,2 tested 259 young women aged
One study, published recently in the jour- rate for vaccine-type HPV decreased signifi- 13-21 for HPV during clinic visits for their first
nal Pediatrics,1 showed a significant decrease cantly from 31.7 to 13.4%. The decrease was vaccine dose. Among 190 who were sexually
in the prevalence of vaccine-type HPV among seen among vaccinated (31.8 to 9.9%), but also active, 70% were already infected. Even girls
vaccinated young women and evidence of among the unvaccinated (30.2 to 15.4%) post- who had sexual contact without intercourse
herd protection in unvaccinated women. surveillance study participants. For vaccinated were at risk, with 11% testing positive for the
Researchers from the Cincinnati Children’s post-surveillance study participants, there was virus.
Hospital Medical Center in Ohio compared a significant increase in nonvaccine-type HPV The three-dose vaccine, proven to reduce
prevalence rates of HPV in young women (60.7 to 75.9%). the risk of HPV infection, is recommended for
before and after HPV vaccine introduction. The authors conclude that four years after 11 and 12 year old girls, according to the CDC.
Females aged 13-26 years who had had sexual licensing of the quadrivalent HPV vaccine, a But some doctors delay the shots, thinking
contact were recruited for a pre-vaccination substantial decrease in vaccine-type HPV prev- pre-teens have a low risk for sexually transmit-
study in 2006-7 (368 women; 0% vaccinated) alence and evidence of herd protection were ted infection.
and a post-vaccination study in 2009-10 observed. The increase in nonvaccine-type

1368 Human Vaccines & Immunotherapeutics Volume 8 Issue 7

 “It really is important for physicians to offer if we can give it to girls and boys before they’re genital warts and cancers of the vulva, vagina,
the vaccine as recommended to girls that sexually active.” penis, anus and throat.
are 11 and 12 years old,” said Dr. Lea Widdice, Dr. Widdice warns that the vaccine can only
assistant professor of adolescent medicine at prevent the infection but cannot cure some- Reference
Cincinnati Children’s Hospital Medical Center one who is already HPV-positive. Thus, early 1. Kahn JA. Pediatrics 2012; 130:e249-56.
and lead author of the study. „The vaccine is vaccination is key to reduce HPV infection, 2. Arch Pediatr Adolesc Med 2012; 166:774-6.
very safe and highly effective, but it works best which beyond cervical cancer is also linked to

First vaccine for visceral leishmaniasis starts human testing

Human trials of the first vaccine against leish- for sand flies. Climate change may also be a to the world’s poor. Drug resistance is also
maniasis, developed by the Infectious Disease factor. Leishmaniasis is still rare in the US, but rising. The Bill & Melinda Gates Foundation is
Research Institute (IDRI) in Seattle, have locally contracted cases have been reported funding the work on IDRI’s new vaccine, which
started. After more than 20 years of research, in south-central Texas and more recently in is designed to fight the most serious form of
the non-profit organization is testing its vac- the northern part of the state. The disease the disease, visceral leishmaniasis. Dr. Steve
cine in three dozen volunteers in Tacoma, comes in many forms, the most common one Reed, founder of IDRI, is optimistic the new
Washington. The vaccine’s safety will also be being a cutaneous infection resulting in pain- vaccine could be ready for market in five years.
tested in India later this year. If found safe, the ful skin lesions that are slow to heal and Researchers at IDRI are seeking cures for
vaccine will be studied in a larger popoluation leave disfiguring scars. In the most dangerous several neglected diseases, but leishmaniasis
in India to determine its efficacy. manifestation, called visceral leishmaniasis (or is the one that they have worked on longest.
The parasite Leishmania is spread to black fever), parasites attack the liver, spleen To manufacture the vaccine for clinical trials
humans by sand flies. It is estimated that and bone marrow. Victims suffer from anemia, in Asia and for commercial distribution, IDRI
more than 12 million people worldwide are fever and a weakened immune system that partnered with an Indian pharmaceutical com-
infected with Leishmania. India, Bangladesh leaves them vulnerable to other infections. pany. India has more leishmaniasis cases than
and Brazil are among the countries where Pigments from ruptured blood cells can turn any other country, and it is important to keep
the virulent version of the pathogen is most the skin dark, hence the name “black fever.” the cost of the vaccine low so it can reach the
prevalent. But the WHO says the disease is Treatments for leishmaniasis exist, but most people in need.
spreading as a result of deforestation, irriga- have serious side effects or are not accessible
tion and dam building that expand habitat

CDC prepares vaccine for new swine flu strain

The emergence of a new strain of „swine flu“ H1N1 pandemic virus. “This ‘m’ gene may con- person-to-person transmission of the virus has
has prompted the CDC to prepare a H3N2 fer increased transmissibility to and among not yet been documented.
candidate vaccine, which will be tested in the humans, compared with other variant influ- There is not yet a cause for alarm, accord-
clinic this year. Up to early August, around 30 enza viruses“, he said. ing to the CDC. “Because influenza viruses are
cases of influenza caused by this new strain Furthermore, the virus appears to have always evolving, we will watch closely for signs
had been identified, but the CDC is making become more active recently. First detected that the virus has gained capacity for efficient
sure it is prepared should the H3N2 strain in humans in July 2011, a total of 29 cases had and sustained human-to human transmission,”
become more widespread. been detected by early August. Looking at the said Dr. Bresee. “Thus far we have not seen
What concerns the CDC about this par- period from July 12 to September 6, 2012, a this type of transmission and therefore are not
ticular virus is that is contains an element seen total of 296 infections with influenza A (H3N2) seeing features consistent with an influenza
in the pandemic 2009 swine flu strain H1N1, variant (H3N2v) virus had been reported pandemic.”
which may make it more likely for the virus to from ten states. For more details and updates
spread from person to person. visit the CDC’s website.1 The vast majority of Reference
In a press conference in early August 2012, cases seem to have occurred after prolonged 1. http://www.cdc.gov/flu/weekly/
Dr. Joseph Bresee from the CDC`s influenza swine exposure, though instances of likely
divison explained that all reported cases were human-to-human transmission have been
infected with strains of H3N2 that contained identified in three cases in 2011. Sustained
the matrix (m) gene from the influenza A

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