High doses of purified influenza A virus hemagglutinin significantly augment serum and nasal secretion antibody responses in healthy young adults.
The reactogenicity and immunogenicity of purified influenza virus hemagglutinin (HA) vaccines administered intramuscularly were evaluated in two placebo-controlled clinical trials. A total of 139 healthy young adults were randomized to receive increasing doses of monovalent influenza A/Taiwan/1/86 (H1N1) virus HA (range, 0 to 405 micrograms per dose [study 1]). An additional 139 subjects were given increasing doses of a trivalent HA vaccine containing equal amounts of A/H1N1 virus, A/Shanghai/16/89 (H3N2) virus, and influenza B/Yamagata/16/88 virus HA (range, 0 to 135 micrograms of HA per strain, 0 to 405 micrograms per dose) or a standard dose of commercial influenza vaccine (study 2). Increasing doses of HA were associated with increasing frequencies of symptoms at the vaccination site early after vaccination, but all doses were well tolerated. Occurrence of systemic symptoms was unrelated to dose. Increasing the dose of HA resulted in increasingly higher postimmunization levels of serum hemagglutination inhibiting and neutralizing antibody levels versus influenza A/H1N1 virus in study 1 (P < 0.05); these enhanced responses persisted for up to 6 months. Nasal secretory immunoglobulin A and G antibody responses were assessed 2 weeks after immunization with monovalent H1N1 virus HA; the frequencies of significant responses also increased in a dose-related fashion. Similar increases in serum antibody levels were noted for both A/H1N1 and A/H3N2 viruses in study 2. These data provide a basis for proceeding with the evaluation of high doses of purified HA in the elderly.
Keitel
W A
WA
Acute Viral Respiratory Disease Unit, Baylor College of Medicine, Houston, TX 77030-3498.
Couch
R B
RB
Cate
T R
TR
Hess
K R
KR
Baxter
B
B
Quarles
J M
JM
Atmar
R L
RL
Six
H R
HR
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000096:biosynthesis*; D004306:Dose-Response Relationship, Immunologic; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology*; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007252:Influenza Vaccines / Q000276:immunology*; D009297:Nasal Mucosa / Q000276:immunology*
D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007252:Influenza Vaccines