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Indian Pediatr 2020;57:594 |
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Clippings
Theme: Immunization |
Vipin
M Vashishtha
Email:
[email protected]
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Vero-cell derived inactivated vaccine candidate for
SARS-Cov-2
(Science. 2020; eabc1932)
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Researchers from Sinovac Biotech, China
developed a pilot-scale production of a purified inactivated
SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced
SARS-CoV-2-specific neutralizing antibodies in mice, rats, and
non-human primates. These antibodies neutralized 10
representative SARS-CoV-2 strains, suggesting a possible broader
neutralizing ability. Three immunizations provided protection in
macaques against SARS-CoV-2 challenge, without observable
antibody-dependent enhancement of infection. The vaccinated
monkeys tolerated well a SARS-CoV-2 virus challenge after 3
weeks of vaccination and none developed a full-blown infection.
The monkeys given the highest dose of vaccine had the best
response. In contrast, four control animals developed high
levels of viral RNA in several body parts and severe pneumonia.
The old-fashioned inactivation methodology used can
be developed easily by many vaccine developers in low- and
middle-income countries, and the absence of lung damage in
vaccinated animals with relatively low levels of antibodies
lessens the concern about vaccine enhancement. However, the
number of animals was too small and the fact that monkeys do not
develop the most severe symptoms that SARS-CoV-2 causes in
humans.
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Oxford Group’s vaccine prevents severe Covid-19
pneumonia in rhesus macaques (bioRxiv.
2020.05.13.093195)
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The Oxford group researchers show that the
adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike
protein of SARS-CoV-2, is immunogenic in mice. A single
vaccination with ChAdOx1 nCoV-19 induced a humoral and cellular
immune response in rhesus macaques. They observed a
significantly reduced viral load in bronchoalveolar lavage fluid
and respiratory tract tissue of vaccinated animals, and no
pneumonia was observed in vaccinated rhesus macaques. At 7 days
post inoculation, all animals were euthanized, and tissues were
collected. Viral genomic (gRNA) was detected in nose swabs from
all animals and no difference in viral load in nose swabs was
found on any days between vaccinated and control animals. None
of the vaccinated monkeys developed pulmonary pathology after
inoculation with SARS-CoV-2. Importantly, no evidence of
immune-enhanced disease following viral challenge in vaccinated
animals was observed.
These observations are marked contrast to the
results reported from Sinovac trial, as the vaccine did not
protect the animals from infection; though, it prevented severe
disease. Thus, the vaccine did not provide sterilizing immunity
to the virus challenge, the gold standard for any vaccine, but
it may provide partial protection. The moot question is that
will partial protection be enough to control the COVID-19
pandemic?
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SARS-Cov-2 infection protects against re-challenge
in rhesus macaques (Science 2020;
science.abc4776)
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An understanding of protective immunity to
SARS-CoV-2 is critical for strategies aimed at ending the
pandemic. A key unanswered question is whether infection with
SARS-CoV-2 results in protective immunity against re-exposure.
Chandrashekar, et al., developed a rhesus macaque model
of SARS-CoV-2 infection and observed that macaques had high
viral loads in the respiratory tract, humoral and cellular
immune responses, and pathologic evidence of viral pneumonia.
Following initial viral clearance, animals were re-challenged
with SARS-CoV-2 and showed 5 log10 reductions in median viral
loads in bronchoalveolar lavage and nasal mucosa compared with
primary infection. Anamnestic immune responses following
re-challenge suggested that protection was mediated by
immunologic control. These data show that SARS-CoV-2 infection
induced protective immunity against re-exposure in nonhuman
primates. However, it should be emphasized that there are
important differences between SARS-CoV-2 infection in monkeys
and humans, with many parameters still yet to be defined in both
species.
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DNA vaccine protection against SARS-CoV-2 in rhesus
macaques
(Science.2020; eabc6284)
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In this study, researchers developed a series
of DNA vaccine candidates expressing different forms of the
SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus
macaques. Vaccinated animals developed humoral and cellular
immune responses, including neutralizing antibody titers
comparable to those found in convalescent humans and macaques
infected with SARS-CoV-2. Following vaccination, all animals
were challenged with SARS-CoV-2, and the vaccine encoding the
full-length S protein resulted in >3.1 and >3.7 log10 reductions
in median viral loads in bronchoalveolar lavage and nasal
mucosa, respectively, as compared with sham controls.
Vaccine-elicited neutralizing antibody titers correlated with
protective efficacy, suggesting an immune correlate of
protection. These data demonstrate vaccine protection against
SARS-CoV-2 in nonhuman primates.
Truly little is known about
immune correlates of protection and protective efficacy of
candidate SARS-CoV-2 vaccines in animal models. In this study,
the researchers demonstrate vaccine protection with substantial
reductions in median viral loads in BAL and nasal swabs, in
immunized animals compared with controls.
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