The antibody responses elicited by immunization of humans with vaccinia virus (VACV) strains Lister, Dryvax and NYVAC have been determined and compared. Neutralizing antibodies against intracellular mature virus (IMV) and extracellular enveloped virus (EEV), and binding antibody titres (ELISA) against the EEV protein B5, the IMV proteins A27 and H3, and VACV-infected cell lysate were measured. Lister and Dryvax induced broadly similar antibody titres, consistent with the fact that these vaccines each protected against smallpox. In contrast, antibody titres induced by NYVAC were significantly lower than those induced by both Lister and Dryvax. Moreover, there were qualitative differences with NYVAC-immunized subjects failing to induce A27-specific antibodies. These observations suggest that although NYVAC is a safer VACV strain, it does not induce an optimal VACV-specific antibody response. However, NYVAC strains engineered to express antigens from other pathogens remain promising candidate vaccines for immunization against other diseases.
AucklandC.,
CowlishawA.,
MorganD.,
MillerE.2005; Reactions to small pox vaccine in naive and previously-vaccinated individuals. Vaccine 23:4185–4187[CrossRef]
BartP. A.,
GoodallR.,
BarberT.,
HarariA.,
Guimaraes-WalkerA.,
KhonkarlyM.,
SheppardN. C.,
BangalaY.,
FrachetteM. J.other authors2008; EV01: a phase I trial in healthy HIV negative volunteers to evaluate a clade C HIV vaccine, NYVAC-C undertaken by the EuroVacc Consortium. Vaccine 26:3153–3161[CrossRef]
BellE.,
ShamimM.,
WhitbeckJ. C.,
SfyroeraG.,
LambrisJ. D.,
IsaacsS. N.2004; Antibodies against the extracellular enveloped virus B5R protein are mainly responsible for the EEV neutralizing capacity of vaccinia immune globulin. Virology 325:425–431[CrossRef]
BelyakovI. M.,
EarlP.,
DzutsevA.,
KuznetsovV. A.,
LemonM.,
WyattL. S.,
SnyderJ. T.,
AhlersJ. D.,
FranchiniG.other authors2003; Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses. Proc Natl Acad Sci U S A 100:9458–9463[CrossRef]
BenhniaM. R.,
McCauslandM. M.,
SuH. P.,
SinghK.,
HoffmannJ.,
DaviesD. H.,
FelgnerP. L.,
HeadS.,
SetteA.other authors2008; Redundancy and plasticity of neutralizing antibody responses are cornerstone attributes of the human immune response to the smallpox vaccine. J Virol 82:3751–3768[CrossRef]
DaviesD. H.,
McCauslandM. M.,
ValdezC.,
HuynhD.,
HernandezJ. E.,
MuY.,
HirstS.,
VillarrealL.,
FelgnerP. L.,
CrottyS.2005; Vaccinia virus H3L envelope protein is a major target of neutralizing antibodies in humans and elicits protection against lethal challenge in mice. J Virol 79:11724–11733[CrossRef]
DaviesD. H.,
WyattL. S.,
NewmanF. K.,
EarlP. L.,
ChunS.,
HernandezJ. E.,
MolinaD. M.,
HirstS.,
MossB.other authors2008; Antibody profiling by proteome microarray reveals the immunogenicity of the attenuated smallpox vaccine modified vaccinia virus ankara is comparable to that of Dryvax. J Virol 82:652–663[CrossRef]
Ferrier-RembertA.,
DrillienR.,
TournierJ. N.,
GarinD.,
CranceJ. M.2008; Short- and long-term immunogenicity and protection induced by non-replicating smallpox vaccine candidates in mice and comparison with the traditional 1st generation vaccine. Vaccine 26:1794–1804[CrossRef]
FreyS. E.,
NewmanF. K.,
YanL.,
LottenbachK. R.,
BelsheR. B.2003; Response to smallpox vaccine in persons immunized in the distant past. JAMA 289:3295–3299[CrossRef]
HammarlundE.,
LewisM. W.,
HansenS. G.,
StrelowL. I.,
NelsonJ. A.,
SextonG. J.,
HanifinJ. M.,
SlifkaM. K.2003; Duration of antiviral immunity after smallpox vaccination. Nat Med 9:1131–1137[CrossRef]
HarariA.,
BartP. A.,
StohrW.,
TapiaG.,
GarciaM.,
Medjitna-RaisE.,
BurnetS.,
CelleraiC.,
ErlweinO.other authors2008; An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses. J Exp Med 205:63–77[CrossRef]
HashizumeS.,
YoshizawaH.,
MoritaM.,
SuzukiK.1985; Properties of attenuated mutant of vaccinia virus, LC16m8, derived from Listre strain. In Vaccinia Viruses as Vectors for Vaccine Antignens pp 87–99 New York: Elsevier Science Publishing Co;
HooperJ. W.,
CusterD. M.,
SchmaljohnC. S.,
SchmaljohnA. L.2000; DNA vaccination with vaccinia virus L1R and A33R genes protects mice against a lethal poxvirus challenge. Virology 266:329–339[CrossRef]
HooperJ. W.,
CusterD. M.,
ThompsonE.2003; Four-gene-combination DNA vaccine protects mice against a lethal vaccinia virus challenge and elicits appropriate antibody responses in nonhuman primates. Virology 306:181–195[CrossRef]
KennedyJ. S.,
FreyS. E.,
YanL.,
RothmanA. L.,
CruzJ.,
NewmanF. K.,
OrphinL.,
BelsheR. B.,
EnnisF. A.2004; Induction of human T cell-mediated immune responses after primary and secondary smallpox vaccination. J Infect Dis 190:1286–1294[CrossRef]
KonishiE.,
KuraneI.,
MasonP. W.,
ShopeR. E.,
Kanesa-ThasanN.,
SmucnyJ. J.,
HokeC. H.Jr,
EnnisF. A.1998; Induction of Japanese encephalitis virus-specific cytotoxic T lymphocytes in humans by poxvirus-based JE vaccine candidates. Vaccine 16:842–849[CrossRef]
LaiC. F.,
GongS. C.,
EstebanM.1991; The purified 14-kilodalton envelope protein of vaccinia virus produced in Escherichia coli induces virus immunity in animals. J Virol 65:5631–5635
LawM.,
PützM. M.,
SmithG. L.2005; An investigetion of the therapeutic value of vaccinia-immune IgG in a mouse pneumonia model. J Gen Virol 86:991–1000[CrossRef]
LustigS.,
FoggC.,
WhitbeckJ. C.,
EisenbergR. J.,
CohenG. H.,
MossB.2005; Combinations of polyclonal or monoclonal antibodies to proteins of the outer membranes of the two infectious forms of vaccinia virus protect mice against a lethal respiratory challenge. J Virol 79:13454–13462[CrossRef]
MayrA.,
MunzE.1964; Changes in the vaccinia virus through continuing passages in chick embryo fibroblast cultures. Zentralbl Bakteriol [Orig] 195:24–35 (in German
McCormackS.,
StohrW.,
BarberT.,
BartP. A.,
HarariA.,
MoogC.,
CiuffredaD.,
CelleraiC.,
CowenM.other authors2008; EV02: a Phase I trial to compare the safety and immunogenicity of HIV DNA-C prime-NYVAC-C boost to NYVAC-C alone. Vaccine 26:3162–3174[CrossRef]
NajeraJ. L.,
GomezC. E.,
Domingo-GilE.,
GherardiM. M.,
EstebanM.2006; Cellular and biochemical differences between two attenuated poxvirus vaccine candidates (MVA and NYVAC) and role of the C7L gene. J Virol 80:6033–6047[CrossRef]
ParrinoJ.,
McCurdyL. H.,
LarkinB. D.,
GordonI. J.,
RuckerS. E.,
EnamaM. E.,
KoupR. A.,
RoedererM.,
BailerR. T.other authors2007; Safety, immunogenicity and efficacy of modified vaccinia Ankara (MVA) against Dryvax challenge in vaccinia-naive and vaccinia-immune individuals. Vaccine 25:1513–1525[CrossRef]
PulfordD. J.,
GatesA.,
BridgeS. H.,
RobinsonJ. H.,
UlaetoD.2004; Differential efficacy of vaccinia virus envelope proteins administered by DNA immunisation in protection of BALB/c mice from a lethal intranasal poxvirus challenge. Vaccine 22:3358–3366[CrossRef]
PutzM. M.,
AlberiniI.,
MidgleyC. M.,
ManiniI.,
MontomoliE.,
SmithG. L.2005; Prevalence of antibodies to Vaccinia virus after smallpox vaccination in Italy. J Gen Virol 86:2955–2960[CrossRef]
PutzM. M.,
MidgleyC. M.,
LawM.,
SmithG. L.2006; Quantification of antibody responses against multiple antigens of the two infectious forms of Vaccinia virus provides a benchmark for smallpox vaccination. Nat Med 12:1310–1315[CrossRef]
StienlaufS.,
ShoreshM.,
SolomonA.,
Lublin-TennenbaumT.,
AtsmonY.,
MeirovichY.,
KatzE.1999; Kinetics of formation of neutralizing antibodies against vaccinia virus following re-vaccination. Vaccine 17:201–204[CrossRef]
TartagliaJ.,
PerkusM. E.,
TaylorJ.,
NortonE. K.,
AudonnetJ. C.,
CoxW. I.,
DavisS. W.,
van der HoevenJ.,
MeignierB.other authors1992; NYVAC: a highly attenuated strain of vaccinia virus. Virology 188:217–232[CrossRef]
TreanorJ.,
WuH.,
LiangH.,
TophamD. J.2006; Immune responses to vaccinia and influenza elicited during primary versus recent or distant secondary smallpox vaccination of adults. Vaccine 24:6913–6923[CrossRef]
XiaoY.,
Aldaz-CarrollL.,
OrtizA. M.,
WhitbeckJ. C.,
AlexanderE.,
LouH.,
DavisH. L.,
BracialeT. J.,
EisenbergR. J.other authors2007; A protein-based smallpox vaccine protects mice from vaccinia and ectromelia virus challenges when given as a prime and single boost. Vaccine 25:1214–1224[CrossRef]